Intraocular implants and related kits and methods

ABSTRACT

Devices, methods and kits are described for reducing intraocular pressure. The devices include a support that is implantable within Schlemm&#39;s canal and that may restore or maintain at least partial patency of the canal without substantially interfering with transmural or transluminal fluid flow across the canal. The devices utilize the natural drainage process of the eye and may be implanted with minimal trauma to the eye. Kits may include a support and an introducer for implanting the support within Schlemm&#39;s canal. Methods may include implanting a support within Schlemm&#39;s canal, where the support is capable of restoring or maintaining at least partial patency of the canal without substantial interference with transmural or transluminal fluid flow across the canal.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/301,874, filed on Feb. 5, 2010, the disclosure of which isincorporated herein by reference in its entirety.

FIELD

The devices, kits and methods described herein relate generally tointraocular pressure reduction. More particularly, the devices, kits andmethods relate to intraocular implants implantable into Schlemm's canalthat can reduce intraocular pressure without substantially interferingwith fluid flow across or within Schlemm's canal, such as transluminalfluid flow, transmural fluid flow, and longitudinal fluid flow.

BACKGROUND

Glaucoma is a potentially blinding disease that affects millions ofpeople worldwide. Typically, glaucoma is characterized by elevatedintraocular pressure. Increased pressure in the eye can cause damage tothe optic nerve which can lead to permanent vision loss if leftuntreated. Consistent reduction of intraocular pressure can slow down orstop the progressive loss of vision associated with glaucoma. Inaddition, patients are often diagnosed with pre-glaucoma and ocularhypertension when they exhibit symptoms likely to lead to glaucoma, suchas somewhat elevated intraocular pressure, but do not yet showindications of optic nerve damage. Treatments for glaucoma, pre-glaucomaand ocular hypertension primarily seek to reduce intraocular pressure.

Increased intraocular pressure is caused by sub-optimal efflux ordrainage of fluid (aqueous humor) from the eye. Aqueous humor or fluidis a clear, colorless fluid that is continuously replenished in the eye.Aqueous humor is produced by the ciliary body, and then flows outprimarily through the eye's trabecular meshwork. The trabecular meshworkextends circumferentially around the eye at the anterior chamber angle,or drainage angle, which is formed at the intersection between theperipheral iris or iris root, the anterior sclera or scleral spur andthe peripheral cornea. The trabecular meshwork feeds outwardly intoSchlemm's canal, a narrow circumferential passageway generallysurrounding the exterior border of the trabecular meshwork. Schlemm'scanal is the eye's primary drainage vessel. Positioned around andradially extending from Schlemm's canal are aqueous veins or collectorchannels that receive drained fluid. The net drainage or efflux ofaqueous humor can be reduced as a result of decreased facility ofoutflow, decreased outflow through the trabecular meshwork and canal ofSchlemm drainage apparatus, increased episcleral venous pressure, orpossibly, increased production of aqueous humor. Aqueous humor flow outof the eye can be restricted by blockages or constriction in thetrabecular meshwork and/or Schlemm's canal. When such flow is blocked,increased ocular pressure may result. Increased intraocular pressure canlead to the collapse of Schlemm's canal. This, in turn, may result in adramatic further increase in intraocular pressure and, ultimately, theonset of glaucoma.

Glaucoma, pre-glaucoma and ocular hypertension currently can be treatedby reducing intraocular pressure using one or more modalities, includingmedication, incisional surgery, laser surgery, cryosurgery, and otherforms of surgery. In the United States, medications or medical therapyare typically the first lines of therapy. If medical therapy is notsufficiently effective, more invasive surgical treatments may be used.In other countries, such as those with socialized medical systems orwith nationalized health care systems, surgery may be the first line oftherapy if it is considered a more cost effective treatment.

A standard incisional surgical procedure to reduce intraocular pressureis trabeculectomy, or filtration surgery. This procedure involvescreating a new drainage site for aqueous humor. Instead of naturallydraining through the trabecular meshwork, a new drainage pathway iscreated by removing a portion of sclera and trabecular meshwork at thedrainage angle. This creates an opening or passage between the anteriorchamber and the subconjunctival space that is drained by conjunctivalblood vessels and lymphatics. The new opening may be covered with scleraand/or conjuctiva to create a new reservoir called a bleb into whichaqueous humor can drain. However, trabeculectomy carries both long andshort term risks. These risks include blockage of the surgically-createdopening through scarring or other mechanisms, hypotony or abnormally lowintraocular pressure, expulsive hemorrhage, hyphema, intraocularinfection or endophthalmitis, shallow anterior chamber angle, andothers.

Bypass stents are also used to bridge a blocked trabecular meshwork.Stents can be inserted between the anterior chamber of the eye andSchlemm's canal, bypassing the trabecular meshwork. However, it isdifficult to consistently and reliably implant a bypass stent from theanterior chamber into Schlemm's canal. The implant procedure ischallenging and stents can become clogged and lose functionality overtime. Others have inserted tubular elongated cylindrical hollow stentslongitudinally into Schlemm's canal. Cylindrical hollow stents can beconfigured to allow circumferential fluid flow around the canal. Thesetoo can lose functionality over time as a result of occlusion orscarring.

Schlemm's canal is small (e.g., approximately 100 microns to 300 micronsin cross-sectional diameter) and circular. Therefore, it can bedifficult or expensive to design and manufacture hollow tubular stentsof appropriate dimensions for use in opening Schlemm's canal. Inaddition, hollow tubular stents can be prone to failure and collapse orocclusion over time, as has been shown for cardiovascular stents. Hollowtubular stents incorporating thin walls are especially prone to failure.Further, the walls of tubular stents placed lengthwise along Schlemm'scanal can have significant surface area contact with the trabecularmeshwork and/or the collector channels, which can result in blockage ofthe meshwork or collector channels, substantially interfering withtransmural flow across the walls of Schlemm's canal and into the eye'scollector channels, and with transluminal flow across the lumen ofSchlemm's canal, thereby preventing restoration of normal eye drainage.

In view of the above, easily manufacturable, minimally invasive devicesfor effective, long-term reduction in intraocular pressure aredesirable. In addition, methods and kits incorporating such devices aredesirable.

SUMMARY

Described here are devices, kits and methods for reducing intraocularpressure. The devices for reducing pressure within the eye comprise asupport implantable circumferentially within at least a portion ofSchlemm's canal, where the support is configured to restore or maintainat least partial patency of at least a portion of the canal. The supportmay have minimal surface area contact with the interior surface of thecanal. This may, for example, allow the support to restore or maintainat least partial patency of the canal without substantially interferingwith transmural or transluminal flow across the canal. The support mayallow for good aqueous humor flow across the trabecular meshwork, acrossSchlemm's canal, and into the collector channels. The support may avoidsubstantial interference with aqueous humor flow by minimizing contactwith, or obstruction of, the inner lumen of Schlemm's canal, and therebyallowing maximum transmural outflow of aqueous humor. The support maythereby utilize and restore the eye's natural drainage pathways.

The support may be capable of implantation into Schlemm's canal withminimal trauma to the eye and in a minimally invasive procedure.Additionally, the support may be relatively easily implanted into theeye, whether by glaucoma specialists or general ophthalmologists, forexample. In some variations, the support may occupy at least a portionof a central core of Schlemm's canal. In certain variations, the supportmay completely traverse the central core of Schlemm's canal.

The support may contact at least one wall portion (e.g., two wallportions) of Schlemm's canal. As an example, the support may contactfirst and second interior wall portions of Schlemm's canal, where thefirst interior wall portion is coincident with an outer peripheralboundary of the trabecular meshwork, and the second interior wallportion has collector channels extending therefrom. In some variations,the support may have minimal surface area contact with the interiorsurface of Schlemm's canal by only tangentially touching the interiorsurface, and may position the majority of its mass in the central coreof Schlemm's canal.

The support may comprise one or more biocompatible materials. As anexample, at least a portion of the support may comprise one or morebiocompatible polymers. Non-limiting examples of polymers which may beappropriate include acrylics, silicones, polymethylmethacrylate,polypropylene, and hydrogels. In addition, at least part of the support(e.g., all of the support) may comprise one or more biocompatiblemetals, such as gold or titanium, and/or one or more biocompatible metalalloys, such as stainless steel or nickel-titanium alloys (e.g.,Nitinol). In some variations, at least a portion of the support maycomprise one or more shape-memory materials. Suitable shape-memorymaterials include, but are not limited to, shape-memory polymers orshape-memory alloys, such as nickel-titanium alloys (e.g., Nitinol). Incertain variations (e.g., certain variations in which a shape-memorymaterial is used), the support may have a compressed state prior to andduring implantation into Schlemm's canal, and an expanded statefollowing implantation (e.g., to open the canal). This may, for example,allow for relatively easy and/or efficient delivery and placement of thesupport into Schlemm's canal.

In some variations, the support may comprise one or more biocompatible,biodegradable polymers. A biodegradable polymer may be, for example,collagen, a collagen derivative, a poly(lactide); a poly(glycolide); apoly(lactide-co-glycolide); a poly(lactic acid); a poly(glycolic acid);a poly(lactic acid-co-glycolic acid); a poly(lactide)/poly(ethyleneglycol) copolymer; a poly(glycolide)/poly(ethylene glycol) copolymer; apoly(lactide-co-glycolide)/poly(ethylene glycol) copolymer; apoly(lactic acid)/poly(ethylene glycol) copolymer; a poly(glycolicacid)/poly(ethylene glycol) copolymer; a poly(lactic acid-co-glycolicacid)/poly(ethylene glycol) copolymer; a poly(caprolactone); apoly(caprolactone)/poly(ethylene glycol) copolymer; a polyorthoester; apoly(phosphazene); a poly(hydroxybutyrate) or a copolymer including apoly(hydroxybutyrate); a poly(lactide-co-caprolactone); a polycarbonate;a poly(esteramide); a polyanhydride; a poly(dioxanone); a poly(alkylenealkylate); a copolymer of polyethylene glycol and a polyorthoester; abiodegradable polyurethane; a poly(amino acid); a polyetherester; apolyacetal; a polycyanoacrylate; a poly(oxyethylene)/poly(oxypropylene)copolymer; or a blend or copolymer thereof.

In certain variations, the support may comprise one or more activeagents. For example, a support may be coated or impregnated with anactive agent. Alternatively or additionally, an active agent may bedispersed within the support (e.g., by filling a cavity within thesupport). An active agent may include a prostaglandin, a prostaglandinanalog (e.g., latanoprost), a beta blocker, an alpha-2 agonist, acalcium channel blocker, a carbonic anhydrase inhibitor, a growthfactor, an anti-metabolite, a chemotherapeutic agent, a steroid, anon-steroidal anti-inflammatory agent, an antagonist of a growth factor,or a combination thereof. The release of an active agent may becontrolled using a time-release system (e.g., by embedding and/orencapsulating the active agent within a time-release composition).

In some variations, the support may be solid, while in other variations,at least a portion of the support may be hollow or porous. The surfaceof the support may be smooth, rough, spiked, and/or fluted, and/or mayhave one or more other modifications. In certain variations, at leastpart of the support may comprise a mesh. The support may include atleast one fenestration and/or one or more rod-like members in somevariations.

In certain variations, the support may comprise at least two adjacentbeads and/or other elements. Adjacent beads or other elements may havethe same or different sizes and/or shapes, and may comprise the same ordifferent materials. Beads and other elements may be spherical,spheroid, ovoid, cylindrical, cuboid, cubical, conical, discoid,helical, or segments thereof, or may have any other appropriate shape.In some variations, a support may comprise a connector linking at leasttwo adjacent beads and/or other elements together. The connector may berigid or flexible. Connectors, beads and/or other elements may becoupled (e.g., attached) to each other or may be integral with eachother. If there is more than one connector (e.g., two connectorsinserted between three beads), the connectors may be of the same ordifferent lengths. The connectors may comprise the same material ormaterials as the beads they connect, or the connectors and beads maycomprise different materials. In certain variations, a connector mayfunction as a spacer configured to provide space between adjacent beads.In some variations, the support may comprise at least two discsseparated by, and connected with, a connector. The discs may includefenestrations. The connector may also comprise a guide wire over which afenestrated bead may be threaded into Schlemm's canal.

In some variations, the support may comprise one or more portions, suchas elongated members, which may be straight, curved, twisted, tubular,fenestrated, fluted, porous, etc., and at least some of which may beintegral with each other and/or coupled to each other. In some suchvariations, the portions may have fenestrated fins and/or bluntserrations, and/or may have one or more edges which may be straight,fluted, curvy, arched, or the like. In certain variations, the supportmay comprise one or more wires which may be straight and/or shaped intovarious configurations. The surface of a wire in the support may besmooth, or may have one or more modifications.

In certain variations, a device for reducing intraocular pressure maycomprise a support implantable circumferentially within at least aportion of Schlemm's canal and configured to restore or maintain atleast partial patency of at least a portion of Schlemm's canal, wherethe support comprises a ribbon member.

In some variations, the ribbon member may comprise at least onefenestration (e.g., multiple fenestrations, such as 2, 3, 4, 5, 10, 15,20, 21, 22, 23, 24 or 25 fenestrations) and/or may be twisted and/orcurved. The ribbon member may comprise a first elongated edge and asecond elongated edge, where the first and second elongated edges areconfigured to contact (e.g., to continuously contact) an interiorsurface of Schlemm's canal when the device is implanted in Schlemm'scanal. The device may not substantially interfere with transmural,transluminal and/or longitudinal flow along, within or across Schlemm'scanal, when the device is implanted in Schlemm's canal. The ribbonmember may be flat. In certain variations, the support may comprise ashape memory alloy, such as a nickel-titanium alloy (e.g., Nitinol). Insome variations, the support may comprise a metal alloy, such asstainless steel or a nickel-titanium alloy (e.g., Nitinol). In certainvariations, the support may comprise a metal, such as titanium.

In some variations, a device for reducing intraocular pressure maycomprise a support implantable circumferentially within at least aportion of Schlemm's canal and configured to restore or maintain atleast partial patency of at least a portion of Schlemm's canal, wherethe support comprises a twisted ribbon member comprising at least onefenestration. In certain variations, a device for reducing intraocularpressure may comprise a support implantable circumferentially within atleast a portion of Schlemm's canal and configured to restore or maintainat least partial patency of at least a portion of Schlemm's canal, wherethe support comprises a twisted ribbon member comprising a plurality offenestrations. In some variations, a device for reducing intraocularpressure may comprise a support implantable circumferentially within atleast a portion of Schlemm's canal and configured to restore or maintainat least partial patency of at least a portion of Schlemm's canal, wherethe support comprises a twisted ribbon member comprising anickel-titanium alloy and a plurality of fenestrations. In certainvariations, a device for reducing intraocular pressure may comprise asupport implantable circumferentially within at least a portion ofSchlemm's canal and configured to restore or maintain at least partialpatency of at least a portion of Schlemm's canal, where the supportcomprises a twisted ribbon member comprising stainless steel and aplurality of fenestrations. In some variations, a device for reducingintraocular pressure may comprise a support implantablecircumferentially within at least a portion of Schlemm's canal andconfigured to restore or maintain at least partial patency of at least aportion of Schlemm's canal, where the support comprises a twisted ribbonmember comprising titanium and a plurality of fenestrations. In certainvariations, a device for reducing intraocular pressure may comprise asupport implantable circumferentially within at least a portion ofSchlemm's canal and configured to restore or maintain at least partialpatency of at least a portion of Schlemm's canal, where the supportcomprises a twisted and curved ribbon member comprising a plurality offenestrations. In some variations, a device for reducing intraocularpressure may comprise a support implantable circumferentially within atleast a portion of Schlemm's canal and configured to restore or maintainat least partial patency of at least a portion of Schlemm's canal, wherethe support comprises a twisted and curved ribbon member comprising anickel-titanium alloy and a plurality of fenestrations.

In certain variations, a device for reducing intraocular pressure maycomprise a support implantable circumferentially within at least aportion of Schlemm's canal and configured to restore or maintain atleast partial patency of at least a portion of Schlemm's canal, wherethe support comprises a twisted ribbon member comprising at least onefenestration, and the device does not substantially interfere withtransmural, transluminal and/or longitudinal flow across, within oralong Schlemm's canal, when the device is implanted in Schlemm's canal.In some variations, a device for reducing intraocular pressure maycomprise a support implantable circumferentially within at least aportion of Schlemm's canal and configured to restore or maintain atleast partial patency of at least a portion of Schlemm's canal, wherethe support comprises a twisted ribbon member comprising a plurality offenestrations, and the device does not substantially interfere withtransmural, transluminal and/or longitudinal flow across, within oralong Schlemm's canal, when the device is implanted in Schlemm's canal.In certain variations, a device for reducing intraocular pressure maycomprise a support implantable circumferentially within at least aportion of Schlemm's canal and configured to restore or maintain atleast partial patency of at least a portion of Schlemm's canal, wherethe support comprises a twisted ribbon member comprising a plurality offenestrations and a nickel-titanium alloy, and the device does notsubstantially interfere with transmural, transluminal and/orlongitudinal flow across, within or along Schlemm's canal, when thedevice is implanted in Schlemm's canal.

In certain variations, a device for reducing intraocular pressure maycomprise a support implantable circumferentially within at least aportion of Schlemm's canal and configured to restore or maintain atleast partial patency of at least a portion of Schlemm's canal, wherethe support has a helical configuration. In some variations, a kit forreducing intraocular pressure may comprise a support implantablecircumferentially within at least a portion of Schlemm's canal andconfigured to restore or maintain at least partial patency of at least aportion of Schlemm's canal, where the support has a helicalconfiguration, and an introducer (e.g., a cannula) for delivering thesupport. Supports having a helical configuration may, for example, be inthe form of a helix or a double helix. In certain variation, the helicesof a double helix may have struts or connecters therebetween. In somevariations, a kit may further comprise instructions on using the kit. Incertain variations, a method for reducing intraocular pressure maycomprise inserting a support circumferentially within at least a portionof Schlemm's canal, where the support is configured to restore ormaintain at least partial patency of at least a portion of Schlemm'scanal, and where the support has a helical configuration. The supportmay, for example, assume the helical configuration after being insertedwithin Schlemm's canal (e.g., as a result of the support beingheat-formed and/or comprising one or more shape-memory materials).

In certain variations, a device for reducing intraocular pressure maycomprise a support implantable circumferentially within at least aportion of Schlemm's canal and configured to restore or maintain atleast partial patency of at least a portion of Schlemm's canal, thesupport comprising a surface (e.g., an outer surface) having a surfacearea. In some variations, less than about 90% (e.g., less than about80%, less than about 70%, less than about 60%, less than about 50%, lessthan about 40%, less than about 30%, less than about 20%, less thanabout 10%, less than about 5%, less than about 3%, less than about 1%)and/or more than about 0.5% (e.g., more than about 1%, more than about3%, more than about 5%, more than about 10%, more than about 20%, morethan about 30%, more than about 40%, more than about 50%, more thanabout 60%, more than about 70%, more than about 80%) of the surface areaof the surface (e.g., outer surface) of the support may contact theinterior surface of Schlemm's canal when the support is in use.

In some variations, a device for reducing intraocular pressure maycomprise a support implantable circumferentially within at least aportion of Schlemm's canal and configured to restore or maintain atleast partial patency of at least a portion of Schlemm's canal, wherethe support comprises a first elongated member comprising a first edgeand a second elongated member comprising a second edge, the secondelongated member coupled to or integral with the first elongated member,and where the first and second edges contact an interior surface ofSchlemm's canal when the support is at least partially disposed withinSchlemm's canal. In certain variations, the support may further comprisea third elongated member comprising a third edge, and the thirdelongated member may be coupled to or integral with the first and secondelongated members.

The support may extend approximately all the way around Schlemm's canal,if the support has a circumference approximately equal to thecircumference of Schlemm's canal. Alternatively, the support may extendaround about 95% or less (e.g., about 85% or less, about 75% or less,about 65% or less, about 50% or less, about 25% or less, about 15% orless, about 10% or less, about 5% or less) of the circumference ofSchlemm's canal. In some variations, the support may extend from 0° to360° (e.g., less than 360°, less than 270°, less than 180°, less than150°, less than 120°, less than 90°, less than 60°, less than 45°, lessthan 30°, less than 15°) around the canal. For example, the support mayextend about 30° to about 180° (e.g., about 50° to about 150°, about 80°to about 120°, about 30° to about 120°, about 100° to about 180°, about120° to about 180°) around the canal. The support may be configured tocontact the inner surface of the walls of Schlemm's canal at one, two,three or more points. In some variations, the support may be attached totissue. The support may comprise a stiff arcuate member having a radiusof curvature smaller or larger than that of Schlemm's canal.

In some variations, the support may be altered using electromagneticradiation. For example, a laser having a wavelength absorbable by atleast one localized portion of the support may be used to alter thesupport. In certain variations, electromagnetic radiation may be used torelease an active agent from the support. In some variations, thesupport may be visually enhanced using fluorescence or phosphorescenceemission. For example, the support may comprise a chromophore thatfluoresces or phosphoresces upon excitation with a light source. In somevariations, the emitted fluorescence or phosphorescence may be in thewavelength range of about 300 nm to about 800 nm. In certain variations,the support may comprise a chromophore that enhances postoperativemonitoring of the support.

Kits for reducing intraocular pressure are also provided. The kits maycontain a support that may be implanted circumferentially withinSchlemm's canal, and that may be configured to restore or maintain atleast partial patency of at least part of Schlemm's canal. When thesupport is at least partially disposed within the canal, the support mayhave minimal surface area contact with the interior surface of thecanal, while also restoring or maintaining at least partial patency ofat least a portion of the canal and not substantially interfering withtransmural, transluminal, and/or longitudinal or circumferential flowacross or within the canal. In some variations, the support may occupyat least a portion of a central core of Schlemm's canal. The kits mayalso contain an introducer for implanting the support within the canal.In certain variations, the kits may include a positioning device foradjusting the support within the canal, instructions for use, and/or oneor more active agents. Some kits may contain at least two supports. Ifmore than one support is included, the kits may include at least twointroducers for delivering the supports. Multiple supports within thesame kit may have the same or different shape, size, or composition.Multiple supports within the same kit may be connected together or mayremain separate. In some variations, kits may include a fixation devicefor attaching a support to tissue. In other variations, kits may includea system for visually enhancing the appearance of the support.

In some variations, a kit for reducing intraocular pressure may comprisea first device comprising a first support implantable circumferentiallywithin at least a portion of Schlemm's canal and configured to restoreor maintain at least partial patency of at least a portion of Schlemm'scanal, the first support comprising a ribbon member, and an introducerconfigured to deliver the first device into Schlemm's canal. Theintroducer may comprise a cannula and/or a pushing member. The kit mayfurther comprise a second device comprising a second support implantablecircumferentially within at least a portion of Schlemm's canal andconfigured to restore or maintain at least partial patency of at least aportion of Schlemm's canal. The first and second supports may havedifferent sizes and/or shapes.

In certain variations, a kit for reducing intraocular pressure maycomprise a first device comprising a first support implantablecircumferentially within at least a portion of Schlemm's canal andconfigured to restore or maintain at least partial patency of at least aportion of Schlemm's canal, the first support comprising a twistedribbon member, and an introducer configured to deliver the first deviceinto Schlemm's canal. In some variations, a kit for reducing intraocularpressure may comprise a first device comprising a first supportimplantable circumferentially within at least a portion of Schlemm'scanal and configured to restore or maintain at least partial patency ofat least a portion of Schlemm's canal, the first support comprising atwisted ribbon member, and a cannula configured to deliver the firstdevice into Schlemm's canal. In certain variations, a kit for reducingintraocular pressure may comprise a first device comprising a firstsupport implantable circumferentially within at least a portion ofSchlemm's canal and configured to restore or maintain at least partialpatency of at least a portion of Schlemm's canal, the first supportcomprising a twisted ribbon member, and a cannula and pushing memberconfigured to deliver the first device into Schlemm's canal. In somevariations, a kit for reducing intraocular pressure may comprise a firstdevice comprising a first support and a second device comprising asecond support, where the first and second supports each are implantablecircumferentially within at least a portion of Schlemm's canal andconfigured to restore or maintain at least partial patency of at least aportion of Schlemm's canal, the first and second supports eachcomprising a twisted ribbon member, and an introducer (e.g., a cannula)configured to deliver the first and second devices into Schlemm's canal.The first and second devices may have the same size or may havedifferent sizes. The first and second devices may have the same shape ormay have different shapes.

Methods for reducing intraocular pressure are also described. Themethods may include inserting a support circumferentially withinSchlemm's canal. The support may be configured to restore or maintain atleast partial patency of at least part of the canal. The support may ormay not occupy at least a portion of a central core of Schlemm's canal,and may not substantially interfere with transmural and/or transluminalflow across the canal, and/or with longitudinal flow within the canal.In some variations, the methods may also include dilating Schlemm'scanal prior to insertion of the support. In certain variations, themethods may comprise anchoring the support to tissue. The methods mayinclude implanting at least two supports. If more than one support isimplanted within a single eye, the multiple supports may be positionedcircumferentially adjacent to each other or circumferentially opposed(i.e., positioned about 180° apart) to each other within Schlemm'scanal. Multiple supports within one eye may be connected or may remainseparate. In some variations of the methods, the support may beilluminated with a light source to visually enhance the position of thesupport. In other variations of the methods, the support may be alteredusing electromagnetic radiation. For example, a laser absorbed by atleast one localized portion of the support may be used to alter thesupport. The alteration may comprise the creation or enlargement of anaperture in the support. If electromagnetic radiation is used to alter asupport, the alteration may occur before implantation or afterimplantation.

In certain variations, a method for reducing intraocular pressure maycomprise inserting a first support comprising a ribbon membercircumferentially within Schlemm's canal, where the first supportmaintains the patency of at least a portion of Schlemm's canal and doesnot substantially interfere with transmural flow across Schlemm's canal.

The method may comprise inserting the first support such that the firstsupport is contained entirely within Schlemm's canal. In somevariations, the first support may traverse at least a portion of acentral core of Schlemm's canal. For example, the first support maycompletely traverse the central core of Schlemm's canal. In certainvariations, the first support may contact first and second interior wallportions of Schlemm's canal, the first interior wall portion beingcoincident with an outer peripheral boundary of the trabecular meshwork,and the second interior wall portion having collector channels extendingtherefrom. The first support may conform to an interior surface ofSchlemm's canal.

The first support may have a first configuration prior to being insertedwithin Schlemm's canal and a second configuration after being insertedinto Schlemm's canal, where the first configuration is different fromthe second configuration. The first support may comprise a shape memoryalloy, such as a nickel-titanium alloy (e.g., Nitinol).

The first support may be inserted within Schlemm's canal using an abinterno approach or an ab externo approach. The method may compriseusing a cannula to insert the first support within Schlemm's canal.

In some variations, the first support may make only tangential contactwith an interior surface of Schlemm's canal when the first support isdisposed within Schlemm's canal. In certain variations, the firstsupport may make only point contacts with an interior surface ofSchlemm's canal when the first support is disposed within Schlemm'scanal. When the first support is disposed within a cylindrical sectionof Schlemm's canal having an internal wall surface area C, the firstsupport may contact less than 30% of C (e.g., less than 25% of C, lessthan 20% of C, less than 15% of C, less than 10% of C, less than 5% ofC, less than 1% of C). The first support may occupy between about ⅛ andabout ½ (e.g., between about ⅛ and about ⅓, between about ¼ and about ½,between about ¼ and about ⅓) of the circumference of Schlemm's canal.

In some variations, the method may further comprise dilating Schlemm'scanal prior to insertion of the first support. In certain variations,the method may further comprise inserting a second supportcircumferentially within Schlemm's canal. Any desired number of supportsmay be inserted within Schlemm's canal to fill any desired amount of thecircumference of the canal, as appropriate. For example, in some casesthe first support may occupy between about ¼ and about ½ (e.g., betweenabout ¼ and about ⅓) of the circumference of Schlemm's canal.

In certain variations, one or more supports described here may bedelivered into Schlemm's canal while the supports are in oneconfiguration, and then may assume a different configuration once thesupports are at least partially disposed within Schlemm's canal. Thismay, for example, provide for relatively easy and efficient delivery andpositioning of the supports within Schlemm's canal. As an example, arelatively straight elongated member (e.g., a wire) formed of one ormore shape-memory alloys may be implanted into Schlemm's canal, and mayassume a helical configuration once the elongated member is at leastpartially disposed within Schlemm's canal. Of course, certain variationsof supports may maintain the same configuration whether within oroutside of Schlemm's canal.

In some variations, supports described herein may restore or maintain atleast partial patency (e.g., full patency) of at least a portion ofSchlemm's canal such that the canal (or at least a portion thereof) hasa diameter of at least about 50 microns (e.g., at least about 75microns, at least about 100 microns, at least about 125 microns, atleast about 150 microns, at least about 175 microns, at least about 200microns, at least about 225 microns, at least about 250 microns, atleast about 275 microns, such as about 300 microns, at least about 350microns, at least about 400 microns, at least about 450 microns) and/orat most about 500 microns (e.g., at most about 450 microns, at mostabout 400 microns, at most about 350 microns, at most about 300 microns,at most about 275 microns, at most about 250 microns, at most about 225microns, at most about 200 microns, at most about 175 microns, at mostabout 150 microns, at most about 125 microns, at most about 100 microns,at most about 75 microns). In some cases, supports described herein maybe used to stretch Schlemm's canal.

In certain variations, a method for reducing intraocular pressure maycomprise inserting a first support comprising a ribbon membercircumferentially within Schlemm's canal such that the first support iscontained entirely within Schlemm's canal, where the first supportmaintains the patency of at least a portion of Schlemm's canal and doesnot substantially interfere with transmural flow across Schlemm's canal.In some variations, a method for reducing intraocular pressure maycomprise inserting a first support comprising a twisted ribbon membercircumferentially within Schlemm's canal, where the first supportmaintains the patency of at least a portion of Schlemm's canal and doesnot substantially interfere with transmural flow across Schlemm's canal.In certain variations, a method for reducing intraocular pressure maycomprise inserting a first support comprising a twisted ribbon membercircumferentially within Schlemm's canal, where the first supporttraverses at least a portion of a central core of Schlemm's canal,maintains the patency of at least a portion of Schlemm's canal and doesnot substantially interfere with transmural flow across Schlemm's canal.In some variations, a method for reducing intraocular pressure maycomprise inserting a first support comprising a twisted ribbon membercircumferentially within Schlemm's canal, where the first supportcompletely traverses a central core of Schlemm's canal, maintains thepatency of at least a portion of Schlemm's canal and does notsubstantially interfere with transmural flow across Schlemm's canal. Incertain variations, a method for reducing intraocular pressure maycomprise inserting a first support comprising a twisted ribbon membercircumferentially within Schlemm's canal, where the first supportcompletely traverses a central core of Schlemm's canal, maintains thepatency of at least a portion of Schlemm's canal and does notsubstantially interfere with transmural flow across Schlemm's canal, andwhere the first support contacts first and second interior wall portionsof Schlemm's canal, the first interior wall portion being coincidentwith an outer peripheral boundary of the trabecular meshwork, and thesecond interior wall portion having collector channels extendingtherefrom. In some variations, a method for reducing intraocularpressure may comprise using a cannula to insert a first supportcomprising a twisted ribbon member circumferentially within Schlemm'scanal, where the first support maintains the patency of at least aportion of Schlemm's canal and does not substantially interfere withtransmural flow across Schlemm's canal.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 provides a partial cross-sectional side view of a normal humaneye.

FIG. 2 provides a partial cross-sectional side view of a normal drainagepath of fluid from the eye.

FIG. 3 shows a front view of normal fluid drainage from the eye.

FIG. 4A shows an alternative front view of normal fluid drainage pathsfrom the eye.

FIG. 4B shows a cross-sectional view along line I-I′.

FIG. 5A provides a front view of an eye in which Schlemm's canal isnarrowed or collapsed, FIG. 5B shows a front view of a device includinga support inserted into Schlemm's canal that allows transmural andtransluminal flow across the canal, and FIG. 5C illustrates an alternatedesign for a device inserted into Schlemm's canal that allows transmuraland transluminal flow across the canal.

FIG. 6A shows side views of various element or bead configurations thatmay be used in the supports described herein, FIG. 6B shows thecorresponding front views of the element or bead configurations shown inFIG. 6A, and FIG. 6C illustrates an element or bead havingfenestrations.

FIG. 7A illustrates a support having multiple juxtaposed beads, FIG. 7Billustrates a support having multiple juxtaposed and connected beads,FIG. 7C shows an alternate configuration of a support having multiplejuxtaposed and connected beads, FIG. 7D shows a support having multiple,spaced-apart but connected beads, and FIG. 7E illustrates beads threadedonto a connector.

FIGS. 8A and 8B show side and front views, respectively, of a supporthaving an open network structure; FIGS. 8C and 8D show side and frontviews, respectively, of a support having a longitudinal zig-zagconfiguration that may contact the wall of Schlemm's canal at leastthree points (labeled P₁, P₂, P₃); FIGS. 8E and 8F show side and frontviews, respectively, of a support having a rod-like member withcontinuously fluted edges and fenestrations; and FIGS. 8G and 8H showside and front views, respectively, of another variation of a supporthaving a rod-like member with continuously fluted edges.

FIGS. 9A and 9B show expanded cross-sectional views of a supportimplanted within Schlemm's canal.

FIGS. 10A-10C illustrate various configurations of supports implantedinto Schlemm's canal.

FIGS. 11A and 11B illustrate two configurations of supports having asmaller radius of curvature than Schlemm's canal, and FIG. 11C shows asupport having a larger radius of curvature than Schlemm's canal.

FIG. 12A illustrates a variation of a support traversing the center ofthe central core of Schlemm's canal; FIG. 12B shows a cross-sectionalview along line II-II′; FIG. 12C illustrates a variation of a supporttraversing the central core of the canal; FIG. 12D shows across-sectional view along line III-III′; FIG. 12E illustrates avariation of a support that occupies the majority of the central core ofthe canal; FIG. 12F shows a cross-sectional view along line IV-IV′; FIG.12G illustrates a variation of support having an open network thatoccupies a portion of the central core of the canal; and FIG. 12H showsa cross-sectional view along line V-V′.

FIGS. 13A and 13B are illustrations of additional variations of supportsthat are implantable within Schlemm's canal.

FIG. 14A is an illustration of another variation of a support that isimplantable within Schlemm's canal, and FIG. 14B is an illustrativedepiction of the support of FIG. 14A positioned within a portion ofSchlemm's canal.

FIGS. 14C-14E depict a variation of a method that may be used to make asupport that is implantable within Schlemm's canal.

FIG. 14F depicts a variation of a component that may be used to make asupport that is implantable within Schlemm's canal.

FIGS. 15A and 15B are illustrative depictions of further variations ofsupports that are implantable within Schlemm's canal.

FIG. 16A is a perspective view of a variation of a component of asupport that is implantable within Schlemm's canal, and FIG. 16B is aperspective view of a variation of a support that is implantable withinSchlemm's canal.

FIGS. 17A-17E are illustrative depictions of variations of supports thatare implantable within Schlemm's canal.

FIG. 18 is an illustrative view of another variation of a support thatis implantable within Schlemm's canal.

FIGS. 19A-19D depict variations of helical supports that are implantablewithin Schlemm's canal.

FIGS. 20A and 20B are illustrative depictions of variations of supportsthat comprise rings and that are implantable within Schlemm's canal.

FIG. 21 depicts a variation of a support that is implantable withinSchlemm's canal.

FIGS. 22A-22E show different variations of supports that are implantablewithin Schlemm's canal.

FIG. 23 shows an illustrative example of a support that may be modifiedusing electromagnetic radiation.

FIG. 24A illustrates a syringe that may be used to insert a support intoSchlemm's canal; FIG. 24B illustrates a variation in which a support isthreaded onto a guide element for insertion and positioning in Schlemm'scanal; FIG. 24C illustrates a cross-sectional view of a support having acentral bore to accommodate a guide element; and FIG. 24D illustrates avariation in which a syringe and a guide element are used for insertionand positioning of a support in Schlemm's canal.

DETAILED DESCRIPTION

Described here are devices, kits and methods to reduce intraocularpressure by restoring or maintaining at least partial patency (e.g.,full patency) of Schlemm's canal, so that at least a portion of thecanal is patent or unobstructed. The devices, kits and methods operateto keep Schlemm's canal from collapsing while not substantiallyinterfering with the eye's natural drainage mechanism for aqueous humor,in which transmural, transluminal and circumferential or longitudinalfluid flow into, across, around and out of Schlemm's canal occurs. Insome variations, the devices may have minimal surface area contact withthe interior surface of Schlemm's canal, when the devices are implantedwithin at least a portion of the canal. The supports may be capable ofmaximizing patency of the canal while minimizing contact with the porousinner wall of the canal and the collector channel-based outer wall ofthe canal. The supports may exhibit minimal or no interference withtransmural flow (across the inner and outer walls of Schlemm'scanal—i.e., into and out of Schlemm's canal), transluminal flow (acrossSchlemm's canal), and/or circumferential or longitudinal flow (alongSchlemm's canal). In some cases, the devices may be implantable inSchlemm's canal with minimal trauma to the eye.

With reference to the figures, FIG. 1 shows a partial cross-sectionalview of the anatomy of a normal human eye. Ciliary body 12 is connectedto iris 18 and to lens 16 via zonular fibrils 14. The anterior chamber20 of the eye is bounded on its anterior (front) surface by cornea 24.In the center of iris 18 is pupil 22. Cornea 24 is connected on itsperiphery to sclera 26, which is a tough fibrous tissue forming thewhite shell of the eye. Trabecular meshwork 28 is located on the outerperipheral surface of anterior chamber 20. The trabecular meshworkextends 360° circumferentially around the anterior chamber. Located onthe outer peripheral surface of meshwork 28 is Schlemm's canal 30.Schlemm's canal extends 360° circumferentially around the trabecularmeshwork. At the apex formed between iris 18, meshwork 28 and sclera 26is angle 32. Conjunctiva 34 is a membrane overlaying sclera 26 andlining the inside of the eyelid (not shown).

FIG. 2 shows a partial cross-sectional view of the flow of aqueous humorwithin and out of a normally functioning human eye. Aqueous humor isproduced in ciliary body 12 and its path through and out of the eye isindicated by solid directional line 36. The aqueous humor flows fromciliary body 12, between lens 16 and iris 18, through pupil 22 intoanterior chamber 20, across trabecular meshwork 28, across Schlemm'scanal 30, into aqueous veins or collector channels (not shown) andfinally into the bloodstream via conjunctival vasculature.

FIG. 3 shows a front view of normal flow of aqueous humor out of theeye. Aqueous humor enters anterior chamber 20 via pupil 22. The fluidflows outwardly toward the periphery of the eye, with the general pathof flow indicated by solid directional lines 36. The fluid crossestrabecular meshwork 28 and traverses Schlemm's canal 30 to reach aqueousveins or collector channels 38. In other words, the fluid flowstransluminally across Schlemm's canal 30, and into collector channels38. There are typically 25-50 (e.g., 25-30) collector channels locatedin a human eye, around the full 360° of Schlemm's canal. The collectorchannels may, for example, each have a diameter of about 25 microns toabout 50 microns. Collector channels 38 are connected to vasculature 40,whereby the drained aqueous humor enters the bloodstream. Although thedirection of net or bulk fluid flow is depicted as radially outward bydirectional lines 36 from pupil 22 for simplicity, actual fluid flow inan eye may follow more varied paths.

Different fluid flow paths in and across Schlemm's canal are illustratedin FIGS. 4A and 4B. FIG. 4A shows a front view of an eye, and FIG. 4Bshows an expanded cross-sectional view along line I-I′. Circumferential(i.e., longitudinal) flow along and around circular canal 30 is depictedby directional lines 50. Fluid that does not traverse canal 30 to reachcollector channels 38 may not be effectively drained from the eye.Examples of fluid flow paths that can effectively drain the eye,including transluminal fluid flow paths (i.e., fluid flow paths thatcross the lumen of Schlemm's canal) are illustrated by directional lines52, 52′, and 52″. In each of these paths, fluid enters trabecularmeshwork 28 along its inner peripheral surface 60 and exits the meshworkalong its outer peripheral surface 62′. Meshwork outer peripheralsurface 62′ provides the inner peripheral surface or wall of Schlemm'scanal 30. Transmural fluid flow across Schlemm's canal involves twoinstances of transmural flow across walls or boundaries. First, fluidmust flow from trabecular meshwork 38 through inner peripheral surfaceor wall 62′ of Schlemm's canal 30 to reach lumen 64 of the canal.Second, fluid must flow from lumen 64 through canal outer peripheralwall 62″ through apertures 38′ to enter collector channels 38. Thus, thefluid must also flow transluminally across the lumen of Schlemm's canal.Finally, the collector channels 38 feed the drained fluid intovasculature. Lumen 64 of canal 30 includes a central core region 67 thatdoes not include the outer periphery of the lumen. As is clearly shownabove, fluid flow from the eye differs from fluid flow in other vesselsin the body where fluid need only flow longitudinally along the vessel,such as blood flowing through a vein.

Devices

Described here are devices for reducing intraocular pressure, where thedevices comprise a support that may be implanted circumferentially inSchlemm's canal to restore or maintain at least partial patency of atleast a portion of the canal. The support may or may not occupy at leasta portion of a central core of Schlemm's canal. In some variations, thesupport may not substantially interfere with transmural and/ortransluminal flow across the canal, and/or with longitudinal flow withinthe canal.

By “restore or maintain at least partial patency” of at least a portionthe canal, it is meant that the support operates to keep at least aportion of the canal at least partially unobstructed to transmural ortransluminal flow, such that fluid can 1) exit through the trabecularmeshwork; 2) traverse the canal; and 3) drain via the collectorchannels. To restore or maintain at least partial patency of the canal,it is not necessary that the support leave the canal unobstructed inregard to circumferential flow. However, supports described here may, ofcourse, be configured to leave the canal unobstructed to circumferentialflow.

By “does not substantially interfere” with transmural flow, it is meantthat the support does not significantly block either fluid outflowacross and from the trabecular meshwork or fluid outflow to and throughthe collector channels. By “does not substantially interfere” withtransluminal flow, it is meant that the support does not significantlyblock fluid flow across the lumen of the canal. In many variations, thesupport may allow between about 0.1 microliter per minute and about 5microliters per minute aqueous outflux from the eye through thetrabecular meshwork and collector channels.

The “central core of Schlemm's canal” refers to the region around thecross-sectional center of the canal in the interior space of the canallumen (i.e., not including the periphery of the canal). Therefore, adevice that occupies at least a portion of a central core of Schlemm'scanal may traverse at least a portion of the canal's lumen. In somecases, a device may completely traverse the central core of Schlemm'scanal.

Additionally, Schlemm's canal includes septae (or endothelial tubules),which are structures that are located periodically through the canal.Without wishing to be bound by theory, it is believed that septae mayserve as structural bridges that help to keep the canal patent, byextending from the inner wall of the canal (a portion of the interiorsurface of the canal that is coincident with an outer peripheralboundary of the trabecular meshwork) to the outer wall of the canal (aportion of the interior surface of the canal having collector channelsextending therefrom). In this way, septae may function similarly tobridge supports. It is believed that over time, septae (e.g., aged orfaulty septae that have weakened or lost their structural integrity) mayhelp to contribute to collapse of Schlemm's canal or portions thereof,in the presence of normal or high pressure. In such cases, devicesdescribed herein may help to replace lost structural septae function,thereby helping to restore or maintain the patency of the canal.

It is also believed that Schlemm's canal in some subjects may includepathologic septae that are essentially walls of scarring that form overtime, compartmentalizing Schlemm's canal and thereby restricting orpreventing longitudinal flow. In such cases, supports described hereinmay have tip portions that are blunted and that may be able to pushthrough the pathologic septae, piercing them and thereby restoringlongitudinal flow. It should be understood that the supports mayalternatively or additionally comprise one or more other features thatmay be capable of disrupting or removing pathologic septae.

Devices described here need not comprise an open-ended tubular supportplaced longitudinally along Schlemm's canal—in other words, the devicesand supports may be non-tubular. A longitudinal, open-ended tubularsupport may enable longitudinal flow along the canal. However, even iffluid can flow longitudinally (i.e., circumferentially) along Schlemm'scanal, the eye may not be effectively drained unless the fluideventually traverses or crosses the canal. That is, transmural fluidflow across two boundaries must occur: 1) fluid must flow from thetrabecular meshwork through a canal inner wall coincident with an outerperipheral boundary of the trabecular meshwork to reach the canal lumen;and 2) fluid must flow from the canal lumen through apertures in thecanal outer peripheral wall to reach the collector channels. Overall,transluminal flow should occur. The collector channels may then furtherdisperse the fluid and complete the natural draining process. A tubularsupport inserted longitudinally into the canal may have significantsurface area overlap with the interior surface of the canal, such thattransmural flow and/or transluminal flow across the canal may besignificantly impeded. A longitudinal tubular support placed inSchlemm's canal may block flow into the canal from the trabecularmeshwork and block flow out of the canal into the collector channels.

Devices described herein for treating elevated intraocular pressureinclude a support that is implanted within Schlemm's canal. In manyinstances, the device may reduce the intraocular pressure by 1-40 mm Hg,for example by at least 2 mm Hg. In other instances, the device mayreduce intraocular pressure by at least 4 mm Hg, or at least 6 mm Hg, orat least 10 or 20 mm Hg. In still other instances, the device mayoperate to bring the intraocular pressure into the range of about 8 toabout 22 mm Hg. The support may be configured in a variety of ways to atleast partially prop open Schlemm's canal, thereby restoring ormaintaining its patency without substantially interfering with orimpeding transmural or transluminal fluid flow across Schlemm's canal.In some variations, the support may not interfere with or blocklongitudinal flow along or around the canal, while in other variationsthe support may interfere with or block longitudinal flow along oraround the canal. In many instances, the support may be containedentirely within Schlemm's canal. In some variations, the support may beimplanted within the canal, but may extend partially beyond Schlemm'scanal (e.g., into the trabecular meshwork and/or into the anteriorchamber).

In certain variations, a support that restores or maintains at leastpartial patency of Schlemm's canal to enable fluid flow between an innerwall of the canal and an outer wall of the canal may comprise elementsor structures such as bead-like elements or beads. The elements orstructures may be connected together (e.g., as a string of beads).Individual elements or beads may be inserted directly into Schlemm'scanal, or a connected group of elements or beads may be inserteddirectly into Schlemm's canal. A more detailed description of supportsincorporating elements or beads is provided below.

FIG. 5A illustrates a front view of an eye having a narrowed orcollapsed Schlemm's canal 30, where canal outer peripheral wall 62″ isvery close to canal inner peripheral wall 62′. Although Schlemm's canal30 is depicted in FIG. 5A as being uniformly narrow around the entirecircumference of canal, it is possible that only a portion of Schlemm'scanal is narrowed or collapsed. When Schlemm's canal is collapsed ornarrowed, net efflux of aqueous from the anterior chamber to thecollector channels 38 is diminished, thereby increasing intraocularpressure. As a result, the risk of pre-glaucoma, ocular hypertension, orglaucoma can increase.

FIG. 5B illustrates an example of a device 70 inserted into Schlemm'scanal 30 through incision site 74. Device 70 in this example ispositioned to one side of incision site 74. Device 70 includes support72, which is configured to keep Schlemm's canal at least partially opento transmural fluid flow across both canal inner wall 62′ and canalouter wall 62″ to reach collector channels 38 via apertures 38′. Support72 may allow for transluminal flow across the canal. In the exampleshown in FIG. 5B, support 72 includes elements or beads 76 connectedwith connectors 78. In this variation, the distance between canal innerwall 62′ and outer wall 62″ is approximately determined by thecross-sectional dimension of support 72, which is in turn determined bythe largest cross-sectional diameter of the beads 76. Therefore,circumferential (i.e., longitudinal) fluid flow around and along thecanal 30 indicated by directional line 50 may be inhibited by theinsertion of support 72 into the canal. However, transmural flow acrossboth walls or boundaries of the canal indicated by directional lines 52,52′, 52″ may be enhanced by support 72, and fluid may be able to reachcollector channels 38 and be drained from the eye. As a result, support72 may effectively reduce intraocular pressure by utilizing the eye'snatural drainage mechanism. Incision 74 need only be large enough toaccommodate the diameter of beads 76, so that trauma to the eye isminimized. Beads or other elements may have cross-sectional dimensionsin the range from about 50 microns to about 500 microns (e.g., about 100microns to about 400 microns, about 200 microns to about 300 microns).Insertion of beads or other elements having relatively smallcross-sectional diameters (e.g., about 50 microns) into Schlemm's canalopens the canal less than the normal cross-sectional diameter of thecanal (which is, for example, approximately 100 microns to 300 micronsin cross-sectional diameter), but may still restore or maintain at leastpartial patency of the canal. Insertion of beads or other elementshaving relatively large cross-sectional diameters (e.g., greater thanabout 300 microns) may open the canal as large as or larger than thecanal's normal cross-sectional diameter and may also operate to stretchthe trabecular meshwork. Stretching the trabecular meshwork may furtherenhance drainage.

FIG. 5C illustrates an alternate configuration of a device 80 insertedinto Schlemm's canal 30 through incision site 84. Device 80 includes asupport 82 that extends to both sides of incision site 84. Support 82includes elements or beads 76 connected with connectors 88 and 88′. Inthis example, connector 88′ is of a different length from connectors 88.As in FIG. 5B, beads 76 may impede circumferential (i.e., longitudinal)fluid flow around and along canal 30 indicated by directional line 50.However transmural and transluminal flow across the canal is enhanced bysupport 82 that restores or maintains at least partial patency acrossthe canal and allows fluid to reach collector channels 38. If the beadsare fenestrated or comprise rough, spiked, and/or fluted perimeters (orother similar features), then circumferential fluid flow through oraround the beads may also occur.

Elements or beads used in a support may be hollow and closed structures,open structures, solid structures, porous structures, or any combinationthereof, and may be of any suitable shape. FIGS. 6A and 6B illustrateside and front views, respectively, of exemplary elements or beads thatmay be used in the supports described here. As shown, solid 90 or hollow91, spherical 90, spheroid 92, ovoid 93, conical 94, disk-shaped 95,polyhedral 96, rod-like 97, or beads with fluted edges 98, rough edges,89, or spiked edges 88 may be used. In some instances, it may be desiredto round corners or edges of the beads or elements. As illustrated inFIG. 6C, elements or beads 76 may include fenestrations 99 and 99′.Fenestrations may have any suitable cross-sectional shape, such as roundor quadrilateral. Although a disc-shaped bead 76 is shown in FIG. 6C,any shape of bead can be fenestrated.

As illustrated in the variations shown in FIGS. 7A-7E, two or more beads76 in a support may be adjacent to each other. Adjacent beads may bejuxtaposed (FIG. 7A), connected and juxtaposed (FIGS. 7B and 7C), orconnected together with connectors 100 and 100′ to form intervalsbetween beads (FIG. 7D). In addition, beads may be threaded onto aconnector 101 (FIG. 7E). Multiple beads used in a single support mayhave the same or different shapes, and may be made of the same ordifferent materials.

Junctions 102 between beads or other elements as shown in FIG. 7B may bemade using any suitable technique, such as by using an adhesive,chemical bonding, mechanical interlocking, and/or welding. Beads orother elements may also be juxtaposed and connected as shown in FIG. 7Cby threading onto a guide element 104. Guide element 104 may comprise afiber, a suture, a guide wire, a fixture, or the like. The beads orother elements may be fixed in a juxtaposed configuration on a guideelement, for example, by knotting ends of the fiber or by providingother end-blocking devices 106, such as clips, caps, protrusions, or thelike on ends 108 of element 104. Any or all of the beads or otherelements may be attached to guide element 104. For example, beads orother elements occupying end positions may be attached to element 104and may function as blocking beads to keep beads from sliding off ends108 of element 104. Alternatively, beads may slide along element 104.Guide element 104 may be flexible, and may be formed of, for example,thin polymer threads, such as a suture, or metal wires. Alternatively,element 104 may be flexible but fixable, such as one or more shapeablemetal wires that may be bent into a desired position and that maymaintain that position against some amount of external stress orpressure. In other variations, guide element 104 may be rigid (e.g., amolded polymeric piece or a stiff metal piece).

As shown in FIG. 7D, multiple connectors 100, 100′ may be used in asingle support, with at least one connector inserted between adjacentbeads 76 or other elements. If multiple connectors are used, they may beof the same or different lengths. In addition, multiple connectorswithin the same support may be made of the same or different materials,and the connectors and beads may be made of the same or differentmaterials. Discrete connectors 100 and 100′ may be inserted betweenbeads 76 and attached to adjacent beads using any suitable methodincluding using adhesives, chemical bonding, welding, mechanicalinterlocking, knots, or any combination thereof. In some variations,connectors 100 and 100′ between beads may be configured to function asspacers between individual beads. As illustrated in FIG. 7E, beads 76may also be threaded onto a connector 101. If the beads are threadedonto a connector, the beads may be maintained in fixed positions alongthe connector 101 by any suitable method, including using adhesives,chemical bonding, welding, clips, protrusions on the connector,mechanical interlocking locking between a connector and a bead, knots,or any combination thereof. Alternatively, some or all beads may slidealong connector 101. Connectors 100, 100′ and 101 may be flexible, suchas thin polymer threads or metal wires. Connectors 100, 100′ and 101 mayalso be flexible but fixable, such as shapeable metal wires.Alternatively, connectors 100, 100′ and 101 may be rigid, such as moldedpolymeric connectors or stiff metal connectors.

Supports of the devices described here need not contain beads. As anexample, a support may comprise one or more other elements, or may be aunitary structure of fixed or variable length. Supports may be solid,hollow, or porous, or any combination thereof. For example, a supportmay be partially solid and partially hollow. Examples of supportconfigurations are shown in side view and front view in FIGS. 8A-8F. Asillustrated in FIGS. 8A and 8B, a support may have an open networkstructure. Such a support may be fabricated out of shapeable metalwires, for example. The support illustrated in FIGS. 8A and 8B may haveminimal surface area contact with the interior surface of Schlemm'scanal—i.e., only point contacts at the end of wires or fibers 170.Alternatively, a support having an open network structure may be atleast partially made from a mesh or foam. The mesh or foam may be madeof any suitable material (e.g., metal and/or plastic). As shown in FIGS.8C and 8D, the support may have a sinusoidal or zig-zag configurationextending along a selected length of Schlemm's canal. For the exampleshown in FIG. 8C, the support may contact the interior surface ofSchlemm's canal at least three points, labeled P₁, P₂, and P₃, afterimplantation. In FIGS. 8E-8H, examples of rod-like supports havingfluted edges are shown. In FIGS. 8E and 8F, fluted edges 110 extendlongitudinally along sides 112 between ends 114 of the support to formstructures 116. Structures 116 may include fenestrations 113. Thesupport may include central bore 117. In FIGS. 8G-H, fluted edges 110′extend along sides 112′ to form structures 116′. Structures 116′ haveserrated outer surfaces 115′ extending between ends 114′. The supportmay include central bore 117′. In the variations illustrated in FIGS.8E-8H, the support may contact the canal walls at least four points. Insome variations, the support may be adjustable. The surface of thesupport may be rough, smooth, spiked or fluted, for example.

A common characteristic of the support configurations described here isthat they need not have continuous or extensive contact with theinterior surface of Schlemm's canal. Indeed, many of the describeddevices and structures may have minimal tangential, periodic, orsporadic contact with the interior surface, and/or may contact theinterior surface only along certain lines and/or at certain points ofthe devices and structures. In some variations, less than about 90%(e.g., less than about 80%, less than about 70%, less than about 60%,less than about 50%, less than about 40%, less than about 30%, less thanabout 20%, less than about 10%, less than about 5%, less than about 3%,less than about 1%) and/or more than about 0.5% (e.g., more than about1%, more than about 3%, more than about 5%, more than about 10%, morethan about 20%, more than about 30%, more than about 40%, more thanabout 50%, more than about 60%, more than about 70%, more than about80%) of the surface area of the outer surface of a support may contactthe interior surface of Schlemm's canal when the support is in use.Devices and structures described here may, for example, havesignificantly less planar contact with the interior surface of Schlemm'scanal than, for example, a hollow tubular stent, such as a hollowtubular cardiovascular stent.

As demonstrated by the example shown in FIGS. 8A and 8B, some supportsonly have point contacts with the interior surface of a canal wall. Forthe supports shown in FIGS. 5B and 5C, the rounded beads of each of thesupports make only tangential contact with the interior surface of acanal wall. Bead shapes may be selected or designed to have minimalsurface area contact with the interior surface of Schlemm's canal. Forexample, beads 98 having fluted edges as shown in FIGS. 6A and 6B mayhave low surface area contact with the interior surface of the canal. Inaddition, supports may have widely spaced apart beads—for example, theconnectors illustrated in FIGS. 7D and 7E may function to space beads atdesired intervals to reduce contact with canal walls yet operate to keepthe canal open. As illustrated above with respect to FIGS. 8C and 8D, insome variations, a support may contact the interior surface of the canalat least two points, or at least three points (e.g., four points, fivepoints, six points, seven points, eight points, nine points, 10 points,etc.).

Expanded cross-sectional views of a support 152 implantedcircumferentially in Schlemm's canal are provided FIGS. 9A and 9B. Thefraction of canal wall surface area in contact with a support can beestimated by viewing the inside of Schlemm's canal as a slightly arcuatecylinder C having length L, extending circumferentially from a first endX₁ to a second end X₂ of support 152, and inside radius R_(i). In somevariations, the support may contact less than 90% (e.g., less than 80%,less than 70%, less than 60%, less than 50%, less than 40%, less than30%, less than 20%, less than 10%, less than 1%, less than 0.1%) of thesurface area of the cylinder C as described above. For example, thesupport 152 shown in FIGS. 9A and 9B contacts the interior surface ofthe canal wall 62 only at bead outer peripheral edges at E₁-E₇, along adistance of the bead width B_(w). There is no contact with the interiorsurface of the canal where connectors 156 space apart beads 154, and nocontact in fluted regions 160 of beads 154. The design feature ofminimal support contact with the interior surface of the canal allows asupport to restore or maintain at least partial patency of the canalwithout substantially interfering with transmural or transluminal flowacross the canal. If a substantial portion of the surface area of theinner periphery of the canal adjacent to the trabecular meshwork or ofthe surface area of the outer periphery of the canal where the collectorchannels are located is blocked, effective fluid flow across or withinthe canal may be impaired.

Supports can have variable lengths and thicknesses. For example, thelength of supports using beads may be adjusted by varying the number,type, or spacing of beads, or any combination thereof. The thickness ofa support may be increased by adding one or more beads having largerdimensions. Unitary supports may also be built with varying lengths, orwith adjustable (e.g., trimmable) dimensions. For example, for a supportmade of shapeable metal having a sinusoidal or zig-zag configuration asshown FIGS. 8C and 8D, a cross-sectional dimension 117 of the supportmay be decreased or increased by, for example, apply tension alongdimension 119.

As illustrated in FIG. 10A, a support 160 may extend essentially aroundthe entire circumference of Schlemm's canal 30. Alternatively, a supportmay extend approximately half way around the circumference of the canal(not shown). As shown in FIG. 10B, a support 162 may extend less thanhalf way around the canal. As shown in FIG. 10C, a support 164 mayextend a quarter or less of the circumference around the canal. Inaddition, more than one support 164, 166, or 168 may be inserted into asingle Schlemm's canal. If multiple supports are inserted into a singlecanal, they can be of different shapes, lengths, materials or sizes, orat least two of the supports can be the same.

A support may be configured such that it will open the canal beyond amaximum cross-sectional dimension of the support itself. For example,FIG. 11A shows a device 130 comprising a support 132 that is insertedinto Schlemm's canal 30. Support 132 comprises beads 134 which have amaximum cross-sectional dimension B_(D). Support 132 comprises a stiffarcuate element 135 with a radius of curvature R_(supp) smaller than theradius of curvature of Schlemm's canal R_(SC). The smaller, fixed radiusof curvature R_(supp) of arcuate member 135 urges canal 30 to open morethan B_(D). In another variation shown in FIG. 11B, support 179comprises an arcuate member 180 without beads having a radius ofcurvature R_(supp) that is less than the radius of curvature R_(SC) ofthe canal. Member 180 is sufficiently stiff to urge the canal open. Inanother variation shown in FIG. 11C, support 181 comprises an arcuatemember 182 having a radius of curvature R_(supp) larger than that ofSchlemm's canal R_(SC). Member 182 is also sufficiently stiff to urgethe canal open. Arcuate members 135, 180 and 182 can comprise a shapememory material such as a nickel-titanium alloy (e.g., Nitinol). Asindicated in FIG. 11C, support 181 can include beads 184. Alternativelyor additionally, a support may include one or more other elements. Tourge open the canal, the radius of curvature R_(supp) of an arcuatemembers can be, for example, at least about 10% (e.g., about 10%, 20%,30%, 40%, or 50%) smaller or larger than that of Schlemm's canal R_(SC).For example, an arcuate member can have a radius of curvature of about 3mm to about 8 mm. In some variations, the radius of curvature of anarcuate member R_(supp) in a support may be at least about 3 mm (e.g.,about 3 mm, or about 4 mm, or about 5 mm). In other variations, theradius of curvature R_(supp) of an arcuate member in a support may be atleast about 6 mm (e.g., about 6 mm, or about 7 mm, or about 8 mm).

As noted above, supports described here may assume a radius of curvaturethat is less or greater than that of Schlemm's canal. In somevariations, a support may assume a radius of curvature that is less orgreater than that of the trabecular meshwork. Moreover, in certainvariations, a support may expand or remodel when at least partiallypositioned within Schlemm's canal. Upon such expansion or remodeling,the support may disrupt the trabecular meshwork or inner wall of thecanal by expanding beyond the diameter of the canal itself. This may,for example, cause the support to push into the trabecular meshwork orpull on it and disrupt it. In some variations, a support may perforatethe walls of the canal or the trabecular meshwork upon expanding and/orremodeling. A support may also perforate the walls of the canal or thetrabecular meshwork upon being delivered to and/or positioned at atarget site.

The supports described here may occupy at least a portion of a centralcore of Schlemm's canal and in some cases may completely traverse thecentral core. The central core of Schlemm's canal is the region aroundthe cross-sectional center of the canal in the interior space of thecanal lumen. A support that occupies at least a portion of the centralcore of the canal can traverse at least a portion of the canal lumen.For example, some variations of supports can traverse thecross-sectional center of the canal at least one point. Referring toFIG. 12A, a front view of a support 220 having beads 222 connected withconnectors 224 is provided. FIG. 12B shows an expanded cross-sectionalview along line II-II′. Support 220 occupies a portion canal centralcore 67 in canal lumen 64. Trabecular meshwork 28 is shown adjacent tocanal 30. In this variation, support 220 traverses the cross-sectionalcenter 66 of the canal. In other variations, supports can traverse thelumen of the canal off-center (e.g., appearing as a chord across thecanal lumen in cross-section). Referring to FIG. 12C, a front view of anarcuate support 210 is shown. FIG. 12D shows an expanded cross-sectionalview along line III-III′. Support 210 traverses and occupies a portionof central core 67 in lumen 64 of canal 30 without passing through canalcenter 66. In some variations, the support may occupy the majority ofthe central core of the canal. Referring to FIG. 12E, a front view ofsupport 230 comprising disc-like beads 232 is shown. A cross-sectionalview along line IV-IV′ is shown in FIG. 12F. As illustrated in FIG. 12F,bead 232 with fenestrations 234 occupies the majority of central core 67of canal 30. In other variations, the support occupies only a smallportion of the central core of the canal. For example, in FIG. 12G, afront view of a support 240 having an open network structure is shown. Across-sectional view along line V-V′ is shown in FIG. 12H.

While certain variations of supports have been described, othervariations of supports having any appropriate configuration may be used.

In some variations, a support may be relatively flat, or may compriseone or more relatively flat components. For example, FIG. 13A shows asupport 1300 comprising a flat ribbon member 1302. As shown, ribbonmember 1302 has multiple fenestrations 1304, although other variationsof supports may comprise ribbon members having fewer fenestrations,fenestrations with different sizes or configurations, or even nofenestrations at all. Moreover, while not shown here, in somevariations, a ribbon member or other support component may have rounded,relatively atraumatic edges. Additionally, supports described here maybe curved or otherwise shaped, such that they are not necessarilystraight and elongated. For example, FIG. 13B shows a support 1320comprising a flat ribbon member 1322 having fenestrations 1324, wherethe flat ribbon member has been twisted into a configuration similar inappearance to a double helix.

FIG. 14A depicts another variation of a support 1400 comprising a ribbonmember 1402 that has been twisted into a configuration similar inappearance to a double helix. As shown there, ribbon member 1402comprises fenestrations 1404 and includes edges 1406 and 1408. FIG. 14Bshows support 1400 disposed within Schlemm's canal 1410, with edges 1406and 1408 contacting the interior surface of the canal. For any givencross-section of Schlemm's canal 1410, support 1400 contacts the canal'sinner wall at two points (i.e., where edges 1406 and 1408 contact thewall). Of course, support 1400 is only one variation of a support andother variations of supports may contact Schlemm's canal at a differentnumber of points for any given cross-section. The two contact points forsupport 1400 rotate as a result of the twisting of support 1400,eventually returning 360° to the same location on the next repeatingunit. In some cases, a support such as support 1400 may complete a full360° turn for every 0.5 millimeter to 2 millimeters (e.g., every 1millimeter to 1.5 millimeters) of the support's length. For example, asupport such as support 1400 may complete a full 360° turn approximatelyevery millimeter of the support's length. Supports may have uniformtwisting, or the degree of twisting of a support may vary along thesupport's length.

A support such as support 1400 may be formed using any appropriatemethod, one of which is depicted in FIGS. 14C-14E.

First, referring to FIG. 14C, a ribbon member 1420 (e.g., formed oftitanium, stainless steel, Nitinol, etc.) is provided (e.g., by cuttinga sheet of the material into individual ribbon members). Ribbon member1420 has a width 1422, a length 1426, and a thickness 1424. In somevariations, width 1422 can be from about 10 microns to about 750 microns(e.g., from about 10 microns to about 600 microns, such as 300 microns),length 1426 can be from about 1 millimeter to about 50 millimeters(e.g., from about 1 millimeter to about 40 millimeters, such as 10millimeters or 15 millimeters), and/or thickness 1424 can be from about10 microns to about 150 microns (e.g., from about 25 microns to about100 microns, such as 50 microns). A ribbon member having a relativelylarge width may, for example, be suitable for use in a procedure thatincludes dilating Schlemm's canal. A ribbon member having a relativelylong length may, for example, be suitable for use in the Schlemm's canalof an eye that has become enlarged as a result of a congenital glaucomacondition. The length of a ribbon member may be selected so that theresulting support occupies a desired amount of the circumference ofSchlemm's canal, such as ⅛ to ½ (e.g., ⅛ to ⅓, ¼ to ½, ¼ to ⅓) of thecircumference of Schlemm's canal.

Next, and as shown in FIG. 14D, the ends of the ribbon member areblunted or rounded, to form a first precursor 1428 to the support, wherethe first precursor has rounded ends 1430 and 1434. The ends may beblunted or rounded using a laser, for example. Blunting or rounding theends of the ribbon member may, for example, render the ribbon memberatraumatic. Ultimately, this may result in a support that iscomparatively less traumatic upon delivery. Additionally, blunted orrounded ends may help to easily guide the support down Schlemm's canal.In some variations, a support may comprise rounded ends that aresemicircular or elliptical, and that have a diameter of about 10 micronsto about 750 microns (e.g., about 10 microns to about 600 microns, suchas 300 microns).

In certain variations, a ribbon member may also be deburred (e.g., toremove slag, cutting materials and oxide).

Referring specifically now to FIG. 14E, fenestrations 1442 are thenformed in the first precursor (e.g., using a laser), thereby forming asecond precursor 1440 to the support. The fenestrations may, forexample, provide for enhanced flow of aqueous humor through and acrossSchlemm's canal when the support is positioned within Schlemm's canal.Fenestrations 1442 each have a width 1444 and a length 1446, and eachfenestration is separated from its neighboring fenestration by adistance 1448. In certain variations, width 1444 may be from about 1micron to about 600 microns (e.g., 125 microns, 150 microns), length1446 may be from about 1 micron to about 5000 microns (e.g., from about1 micron to about 500 microns, such as 300 microns), and/or distance1448 may be from about 1 micron to about 5000 microns (e.g., from about1 micron to about 300 microns, such as 150 microns). Of course, whilefenestrations 1442 are depicted as each having the same size and beinglocated at the same distance from the next fenestration, in somevariations, a support may comprise fenestrations of different sizesand/or fenestrations that are separated from each other by differentdistances. Moreover, any suitable number of fenestrations may be used.In some variations, a support may not have any fenestrations, or mayhave just one fenestration. In certain variations, a support may havemultiple fenestrations, such as 2, 3, 4, 5, 8, 10, 15, 20 23, 24 or 25fenestrations.

After second precursor 1440 has been formed, the second precursor may betwisted (e.g., around a mandrel, using heat treatment, and or using avise or vise-like tooling), thereby forming support 1440. In somevariations, the twisted support may then be curved, for example, toapproximate the curvature of Schlemm's canal. In some cases, the curvemay be heat-set into the support (e.g., by positioning the support in amold having the desired curvature and heat-treating the support to setthe curve). In certain variations, the support may be curved to a radiusof curvature of about 2 millimeters to about 12 millimeters (e.g., about3 millimeters to about 9 millimeters, or about 4 millimeters to about 8millimeters, such as 6 millimeters). In certain variations, a supportmay not be curved (i.e., the support may be straight).

Additional steps may include electropolishing the support (e.g., tosmooth its surface and edges and render it atraumatic) and/or applying acoating (e.g., heparin) to the support.

It should be understood that any of the features or characteristics ofparticular supports described herein, including methods of making andusing the supports, may be applied to other supports as well, asappropriate.

In variations in which ribbon members are used to form supports, theribbon members may have any suitable size, shape and configuration. Forexample, a ribbon member may or may not include one or morefenestrations, and if the ribbon member includes at least onefenestration, the fenestration may have any appropriate shape, such astriangular, rectangular, square, oval, elliptical, circular, etc. Insome variations, fenestrations may be in the form of lines or slits.Fenestration size and/or shape may be selected, for example, to enhancethe longitudinal strength of the support as it is being positionedwithin Schlemm's canal (e.g., by using circular and/or ellipticalfenestrations). FIG. 14F shows a ribbon member 1450 comprisingatraumatic rounded ends 1452 and 1454, and having staggereddiamond-shaped fenestrations 1456. For any one cross-section of ribbonmember 1450, the amount of ribbon material (e.g., metal) and the amountof fenestration is the same as for any other cross-section of the ribbonmember. This may, for example, provide for symmetrical twisting of theribbon member during formation of the support. Of course, in some casesa ribbon member may include fenestrations (e.g., diamond-shapedfenestrations and/or staggered fenestrations) that do not provide theribbon member with the above-described features and that do not providefor symmetrical twisting of the ribbon member. Additionally, whileribbon member 1450 comprises diamond-shaped fenestrations that are allof the same size, other variations of ribbon members may comprisefenestrations of different shapes and/or sizes. Moreover, fenestrationsmay be arranged in any suitable configuration.

Certain variations of supports may have chain-like configurations. Theindividual chain “links” may be coupled to each other, or at least someof the individual chain “links” may be integral with each other. As anexample, FIG. 15A shows a support 1500 comprising integral chain “link”components, such as component 1502, having a central opening 1504. Ofcourse, as described above, in some variations such a support may betwisted, as is the case with support 1510 in FIG. 15B, which comprisesintegral chain “link” components, such as component 1512 having acentral opening 1514, and which has a twisted configuration.

Any appropriate support components may be used. For example, FIG. 16Ashows a support component 1600 comprising a body 1602 having variouscut-outs (e.g., 1604 and 1606) that may be formed using, for example, amolding or machining process, such as a laser machining process.Component 1600 may, for example, form the entirety of a support, or maybe coupled to, or integrally formed with, one or more identicalcomponents and/or one or more different components, to form a support.In some variations, and as discussed above, various portions of asupport may lie along different planes. As an example, FIG. 16B shows asupport 1610 comprising identical components 1612 and 1614 integrallycoupled to each other by a connector 1616, where each componentcomprises portions lying along different planes (such as portions 1618and 1620 of component 1612).

In some variations, a support may comprise at least one elongatedmember. The elongated member may be straight, curved, bent, etc. Incertain variations, the elongated member may be delivered into Schlemm'scanal in a first configuration (e.g., straight), and then may assume asecond configuration (e.g., curved, helical, double helical, etc.)during and/or after being initially positioned within at least a portionof the canal. For example, FIG. 17A shows a support 1700 comprising anelongated member 1702 in a straight configuration. Elongated member 1702may be formed of, for example, a single wire. Because Schlemm's canal isrelatively small in diameter (e.g., around 150-200 micrometers), it maybe beneficial for a support to be formed of a small wire or wires.

In some variations, a support may be formed of a straight or curved wirethat is inserted into the canal and that passively follows the path ofthe canal. Alternatively, a support may be inserted into the canal as astraight wire, and may then remodel to dilate the canal and restorepatency, or to distend the canal so that it has a different radius ofcurvature. In certain variations, a support may be inserted into a canalas a curved wire, and may then remodel to dilate the canal and restorepatency, or to distend the canal so that it has a different radius ofcurvature. The same effects as described above may be achieved in somevariations with a support comprising multiple wires that may or may notbe connected with each other or integral or unitary. In some variations,a support may be inserted into a canal and may dilate the canal withoutremodeling. For example, a support may be pushed into the canal todilate the canal.

In certain variations, a support may be in the form of a continuous wirethat props open Schlemm's canal or distends the trabecular meshwork onits own. Alternatively, a support may comprise a core comprising acontinuous wire, as well as one or more additional wires and/or otherfeatures stemming from the core, where the additional wire(s) and/orother features prop open the canal or distend the trabecular meshwork.For example, a support may comprise one or more components or elementshaving the shape of a whisk. In certain variations, a support maycomprise a discontinuous wire comprising stretches of a core elementperiodically interrupted by non-core elements that dilate Schlemm'scanal or distend the trabecular meshwork. For example, a support maycomprise a series of core wire elements alternating with a series ofring elements. It should be understood that in any variations ofsupports comprising wire cores, the wire core may be fenestrated and/orotherwise modified.

A wire or other support component may have a cross-section of anyappropriate size and shape. For example, the cross-section of a wire orother support component may be circular, ovoid, planar, square,triangular with arced edges, or may have any other suitable shape.Moreover, a wire or other support component may comprise a smooth andcontinuous surface, a smooth and discontinuous surface (e.g., havingdifferent diameters along its length, different shapes along its length,such as a wire having a circular cross-section that turns planar incertain segments, or having symmetrical or asymmetrical shapes, curves,and/or diameters), or a surface that is not smooth. In variations inwhich the surface is not smooth, the wire or other support componentmay, for example, have continuously fluted edges or multiple edges(e.g., one, two, or three edges) that are parallel along the wire orcomponent, discontinuously fluted edges that are parallel along the wireor component, continuously fluted edges that are perpendicular to thewire or component, discontinuously fluted edges that are perpendicularto the wire or component, continuously fluted edges that are swirled orangled along the wire or component, or discontinuously fluted edges thatare swirled or angled along the wire or component. The periphery of thefluted edges may be bluntly serrated or undulating in some variations.Additionally, in certain variations a support may comprise fins that areboth fluted and fenestrated.

In variations in which wires are used, the wires may have anyappropriate dimensions. For example, a wire may have a diameter of up toabout 500 micrometers (e.g., up to about 400 micrometers, up to about300 micrometers, up to about 200 micrometers, up to about 100micrometers, up to about 50 micrometers, up to about 25 micrometers, upto about 10 micrometers). The wire may alternatively or additionallyhave a diameter of at least about 10 micrometers (e.g., at least about25 micrometers, at least about 50 micrometers, at least about 100micrometers, at least about 200 micrometers, at least about 300micrometers, at least about 400 micrometers). In certain variations, awire may have a relatively thick diameter and may comprise fenestrationsat any appropriate location (e.g., at its core, along its edges, orboth).

In some variations, an elongated member may comprise one or more surfacefeatures or other modifications that may, for example, allow forenhanced transmural and transluminal flow when the support is positionedwithin the canal. As an example, FIG. 17B shows a support 1710comprising an elongated member 1712 having multiple fenestrations 1714.While fenestrations 1714 have the same size and shape and are evenlyspaced relative to each other, some variations of supports may compriseone or more fenestrations and/or other features having different sizesand/or shapes, and/or that are not evenly spaced. FIG. 17C depicts asupport 1720 comprising an elongated member 1722 having multipleapertures 1724 formed therein. Elongated members and portions thereofmay be solid, tubular, or porous, or may have any other appropriateconfigurations. In certain variations, an elongated member may compriseat least one solid portion, at least one tubular portion, and/or atleast one porous portion.

As discussed above, in some variations a support may comprise a curvedelongated member. The elongated member may have just one curve or mayhave multiple curves. As an example, FIG. 17D shows a support 1730comprising a curved elongated member 1732. As shown there, elongatedmember 1732 has just one broad curve. However, FIG. 17E shows a support1740 comprising multiple curved members (e.g., curved members 1742 and1744) that are coupled to each other (e.g., via welding, adhesive,etc.). Of course, while curved members 1742 and 1744 are coupled to eachother, in certain variations a support may alternatively or additionallycomprise multiple curved portions that are integral with each other. Forexample, a support may comprise a single Nitinol wire shaped into asinusoidal curve. The curved portions of a support may lie along thesame plane, as shown in FIG. 17E, or along different planes. Moreover,some supports may comprise multiple curves, with some or all of thecurves lying along the same plane, or some or all of the curves lyingalong different planes. Support 1740 essentially has a sinusoidalconfiguration, although other suitable configurations including multiplecurves may also be used. As an example, FIG. 18 shows a support 1800comprising multiple coupled or integral arcs or arches, such as arch1802. The arches all lie along the same plane, but other variations ofsupports may comprise arches that lie along different planes. Moreover,arches or arcs may or may not be identical in size, radius of curvature,etc.

Other appropriate shapes and configurations may be used for supportsthat are implantable into at least a portion of Schlemm's canal. In somevariations, helical configurations may be used. The configurations maycomprise just one helical shape, or may comprise multiple helicalshapes, such as a double helix. The helical shapes may just tangentiallytouch the interior surface of Schlemm's canal when disposed within thecanal. In this way, they may provide sufficient support to restore ormaintain at least partial patency of at least a portion of the canal,while also avoiding substantially interfering with transmural andtransluminal flow across the canal. As a result, the canal's naturaldrainage passageways may be restored.

FIG. 19A shows an exemplary support having a helical configuration. Asshown there, a support 1900 is in the form of a single helix. FIG. 19Bshows support 1900 within Schlemm's canal 1901, where the support onlytangentially touches the interior surface 1902 of the canal (e.g., atpoints 1903 and 1904). Of course, as discussed above, other helicalconfigurations may alternatively or additionally be used withinSchlemm's canal. As an example, FIG. 19C depicts a support 1920 in theform of a double helix, and FIG. 19D shows support 1920 disposed withinSchlemm's canal 1922. Helices may in some cases have struts and/or otherconnectors therebetween. For example, a double helix may comprise firstand second helices that are connected to each other by struts extendingbetween them.

Supports having helical configurations, as well as other variations ofsupports described here, may be capable of restoring or maintaining atleast partial patency of at least a portion of Schlemm's canal (e.g.,the entirety of the canal) with minimal tangential touch. For example, asupport, when at least partially disposed within the canal, may contactthe interior surface of the canal only at tangent points. Additionally,the majority of a support may occupy the central core of Schlemm'scanal, rather than the very periphery of the canal, and may avoidcontacting the interior surface of the canal. As a result, theobstruction of aqueous flow at the valuable, porous inner and outercanal walls may be minimized or prevented. With restoration of canalpatency and minimal wall obstruction, aqueous humor may again easilytraverse the canal (e.g., in the case of a support having a helicalconfiguration, through the open helical network).

In some variations, a support having a helical configuration, or anothervariation of a support described here, may be delivered at leastpartially into Schlemm's canal and expanded into its final configurationonce the support is at least partially disposed within Schlemm's canal.Upon support delivery and expansion, dilation of the three primary andcritical drainage structures may be restored: (1) juxtacanaliculartissue distension and pore dilation (inner wall), (2) dilation ofSchlemm's canal, and (3) collector channel dilation (outer wall). Ofcourse, such restoration may be achieved with other supports and/ordelivery and positioning mechanisms described here, as well. Withminimal wall obstruction, aqueous humor may again easily traverse thedilated canal lumen and walls through the open helical network.

In certain variations, a support may comprise multiple rings that arecoupled to each other or integral with each other. For example, FIG. 20Ashows a support 2000 comprising multiple rings, such as ring 2002, alllying along the same plane. While the rings all have the same size, somevariations of supports may comprise multiple rings having differentsizes. Moreover, rings may have different shapes. For example, somerings may be rounded and circular, while other rings are oval and havesomewhat beveled edges. Furthermore, some variations of supports maycomprise rings that do not lie along the same plane. As an example, FIG.20B shows a support 2010 comprising multiple rings, such as ring 2012,that are coupled to each other, where adjacent rings are positioned at a90° angle with respect to each other.

Still further variations of supports may be used. For example, FIG. 21shows a support 2100 comprising multiple coupled components, such ascomponent 2102, having a shape similar to an egg beater or whisk, with acentral opening 2104. While each component comprises four curvedportions (such as curved portions 2106, 2108, 2110 and 2112 of component2102), other variations of supports may comprise components having asimilar shape, but a different number of curved portions.

In some variations, a support may comprise one or more edges that areconfigured to contact the interior surface of Schlemm's canal duringuse. For example, FIG. 22A shows a support 2200 comprising threeintegral elongated members 2202, 2204 and 2205. The adjacent elongatedmembers come together at a junction, such as junction 2206 betweenadjacent elongated members 2202 and 2204. When support 2200 is disposedwithin Schlemm's canal, the majority of the support may be locatedwithin the central core of the canal, with the edges of the supporttangentially touching the interior surface of the canal.

Of course, the edges of a support need not necessarily be linear. Forexample, FIG. 22B shows a support 2210 comprising three integralelongated members 2212, 2216 and 2217, where adjacent elongated memberscome together at a junction, such as junction 2218 between adjacentelongated members 2212 and 2216. As shown in FIG. 22B, elongated member2212 has a curvy edge 2214. Such an edge may, for example, haverelatively little contact with the interior surface of Schlemm's canal,while still having sufficient contact to help restore or maintain atleast partial patency of at least a portion of the canal.

The different portions of a support may also comprise one or moremodifications, such as apertures, fenestrations, pores, etc. Forexample, FIG. 22C shows a support 2220 comprising three integralelongated members 2222, 2226 and 2227, where adjacent elongated memberscome together at a junction, such as junction 2228 between adjacentelongated members 2222 and 2226. As shown in FIG. 22C, elongated member2222 comprises multiple apertures 2224. While the apertures are alldepicted as having the same general size and shape, other variations ofsupports may comprise apertures having different sizes and/or shapes.Moreover, some variations of supports may comprise combinations of oneor more of the above-described features, as well as any otherappropriate features. For example, FIG. 22D shows a support 2230comprising a central tubular member 2236 and three integral elongatedmembers 2232, 2234 and 2235 radiating from the central tubular member.Integral elongated member 2232 has a curvy edge 2233, while centraltubular member 2236 comprises multiple apertures 2238. Central tubularmember 2236 may be in the form of, for example, a wire having a lumentherethrough. Of course, while support 2230 comprises a single centraltubular member, in some variations, a support may alternatively comprisemultiple tubular members, or may alternatively or additionally compriseat least one non-tubular elongated member, such as a central non-tubularelongated member (e.g., a central solid wire). The tubular members ornon-tubular elongated members may or may not comprise one or morefeatures, such as apertures, fenestrations, or the like.

While the above-described supports comprise three integral elongatedmembers, it should be understood that supports may comprise any suitablenumber of elongated members and/or other components. For example, asupport may comprise two elongated members and/or other components, ormay comprise more than three elongated members and/or other components.The elongated members and/or other components may also have any numberof edges. Moreover, at least some of the elongated members and/or othercomponents may not be integral with each other. For example, at leasttwo of the elongated members may be coupled (e.g., welded,adhesive-bonded, etc.) to each other. Additionally, any number ofelongated members and/or other components in a support (e.g., all of theelongated members and other components) may comprise features such asfluted edges, curvy edges, fenestrations, apertures, pores, or the like,or any combination thereof. For example, in some variations, a supportmay comprise four elongated members, where each elongated member hasfluted edges and/or fenestrations. A support may also include elongatedmembers and/or other components having different features from eachother.

In certain variations, a support may comprise one or more twisted orotherwise non-linear portions. For example, FIG. 22E shows a support2240 comprising three portions 2242, 2244 and 2246 that are twistedrelative to each other, such that they form a somewhat helicalconfiguration. It should be noted that any other support configurationsshown herein may be twisted upon final assembly, as appropriate. Asshown, the portions may at least partially comprise straight edges,and/or may at least partially comprise edges that are not straight, suchas curvy edge 2247 of portion 2246.

Supports described here may have any suitable dimensions. For example,in some cases a single support may have a length (when curved, an arclength) of 10 millimeters. The dimensions of a support, such as itslength, may depend on clinical need. For example, some patients (e.g.,more severe glaucoma patients) may require multiple supports or longersupports for greater outflow restoration. It should be noted thatmultiple supports may be implanted simultaneously or at different times.In some variations, multiple supports may be used in a procedure,because it may be easier to insert multiple smaller supports rather thanone longer support. As an example, in some variations, two supports thateach have a length of 10 millimeters may be inserted into Schlemm'scanal. Alternatively, in certain variations, one longer support may beused. In some cases, a single support may be used along the entirecircumference of Schlemm's canal.

A support, such as a support comprising one or more wires, may compriseany of a variety of different materials. In general, a support maycomprise one or more biocompatible materials, such as biocompatiblepolymers or plastics, polymer composites, ceramics or ceramiccomposites, glass or glass composites, metals, alloys (e.g.,shape-memory alloys, superelastic alloys) or combinations or derivativesof these materials. Examples of biocompatible metals and metal alloysinclude stainless steel, gold, silver, titanium, tantalum, platinum andalloys thereof, cobalt and chromium alloys, and nickel-titanium alloyssuch as Nitinol. Examples of biocompatible polymers include high densitypolyethylene (HDPE), polyurethane, polycarbonate, polypropylene,polymethylmethacrylate (PMMA), polybutylmethacrylate, polyesters,polytetrafluoroethylene (PTFE), silicone, acrylic polymers, polyvinylalcohol, polyvinyl pyrrolidone, polyvinyl chloride, ethyl vinyl acetate,collagen, collagen derivatives, flexible fused silica, polyolefins,NYLON® polymers, polyimide, polyacrylamide, fluorinated elastomers, andcopolymers and blends thereof. In addition, biocompatible hydrogels maybe used in supports and devices described herein. As discussed in moredetail below, biocompatible polymers may be biodegradable. In somevariations, a component of a support, such as a wire, may comprise oneor more hydrophilic materials, such as those that are used in contactlenses. The hydrophilic material(s), when incorporated into the support,may be capable of restoring or maintaining at least partial patency ofSchlemm's canal and/or distending the trabecular meshwork, absorbingaqueous humor, and/or transferring aqueous humor out of Schlemm's canal.A support may be made of a single material or a combination ofmaterials. In some variations, a support made from a first material maybe coated with a second material (e.g., to enhance or improve itsbiocompatibility).

In some examples, a support may comprise one or more biodegradablepolymers. Examples of suitable biodegradable polymers include collagen,a collagen derivative, a poly(lactide), a poly(glycolide), apoly(lactide-co-glycolide), a poly(lactic acid), a poly(glycolic acid),a poly(lactic acid-co-glycolic acid), a poly(lactide)/poly(ethyleneglycol) copolymer, a poly(glycolide)/poly(ethylene glycol) copolymer, apoly(lactide-co-glycolide)/polyethylene glycol) copolymer, a poly(lacticacid)/poly(ethylene glycol) copolymer, a poly(glycolicacid)/poly(ethylene glycol) copolymer, a poly(lactic acid-co-glycolicacid)/poly(ethylene glycol) copolymer, a poly(caprolactone), apoly(caprolactone)poly(ethylene glycol) copolymer, a polyorthoester, apoly(phosphazene), a poly(hydroxybutyrate) or a copolymer including apoly(hdroxybutyrate), a poly(lactide-co-caprolactone), a polycarbonate,a poly(esteramide), a polyanhydride, a poly(dioxanone), a poly(alkylenealkylate), a copolymer of polyethylene glycol and a polyorthoester, abiodegradable polyurethane, a poly(amino acid), a polyetherester, apolyacetal, a polycyanoacrylate, a poly(oxyethylene)/poly(oxypropylene)copolymer, and blends and copolymers thereof.

At least a portion of a support may be made from a shape-memorymaterial. For example, shape-memory alloys (e.g. a nickel-titaniumalloy) may be used. In addition, shape-memory polymers (e.g., polymersmade from copolymerizing monomers oligo(e-caprolactone) dimethacrylateand n-butyl acrylate or polymers based on styrene acrylate, cyanateester and epoxies) may be used. In some variations in which ashape-memory material is used in the support, the support can have acompressed state prior to and during implantation, and an expanded statefollowing implantation. The use of a compressed state support comprisinga shape-memory material can allow for a smaller incision and facilitateinsertion into a narrowed or compressed Schlemm's canal. Once implanted,the support may be expanded using any suitable method (e.g., thermallyactivated by body heat or an alternate heat source) to adopt an expandedstate, thereby opening the canal.

The support may include one or more active agents, such as apharmaceutical. For example, a support may comprise one or morematerials that function as a depot for one or more active agents.Examples of such materials include those that have been tested in theeye for intraocular lenses, such as polymethylmethacrylate (PMMA),silicone polymers, hydrogels, acrylic polymers, metals (e.g., gold) andalloys (e.g., shape-memory alloys such as Nitinol, superelastic alloys,etc.). Exemplary active agents include prostaglandins, prostaglandinanalogs, beta blockers, alpha-2 agonists, calcium channel blockers,carbonic anhydrase inhibitors, growth factors, such as tissue growthfactors and vascular endothelial growth factors, anti-metabolites,chemotherapeutic agents such as mitomycin-C, 5-fluorouracil, steroids,non-steroidal anti-inflammatory agents, antagonists of growth factorssuch as antagonists of vascular endothelial growth factors, orcombinations thereof. An active agent may be provided as a coating on atleast a portion of a support. An active agent may be deliveredthroughout the eye by dissolution or other dispersal mechanisms.Alternatively, at least a portion of a support may be impregnated withan active agent. In some variations, an active agent may be dispersedwithin at least a portion of a support. For example, a cavity in thesupport may be filled with the active agent.

The delivery of an active agent may be controlled by time-release. Forexample, the portion of a support containing an active agent may includea time-release coating or time-release formulation designed to graduallydissipate the active agent over a certain period of time. Biodegradablecoatings and formulations for time-release of active agents are known inthe art. In certain variations, a support may comprise multiple layers,where the layers each comprise an active agent. For example, supportlayers can be used to release a series of different agents, or a seriesof doses of the same agent. Such layers may be part of a coating appliedto a support, or part of a support body. In addition, a support maycomprise one or more biodegradable layers that do not contain any activeagent, and that may be applied or interspersed between other layers tofurther control delivery of active agents to the eye.

In some variations, it may be desirable to change or alter a supportusing electromagnetic radiation. For example, at least a portion of asupport may be fenestrated, perforated, bent, shaped or formed using alaser to enhance intraocular pressure reduction. As illustrated in FIG.23, predetermined localized portions 120 of a support 122 may bedesigned to absorb light of a certain wavelength or wavelength range.Preferential absorption may be achieved by material selection and/or bydoping with chromophores, for example. Upon irradiation with sufficientenergy at the selected wavelength or wavelength range, the patternedregions 120 may ablate or melt, leaving new or enlarged perforations orindentations in the support. For example, a pulsed titanium sapphirelaser operating between about 750 nm and about 800 nm may be used toablate gold regions. If beads 126 in support 120 are hollow, then afterirradiation and ablation, features 120 may become fenestrations. Thefenestrations may be created to make support 122 more porous in natureand/or to allow release of an active agent from within a support (e.g.,from within beads 126). Alternatively or additionally, it may bepossible to use a mask in combination with electromagnetic radiation toalter a support, such as by patterning or machining. The modification ofa support using electromagnetic radiation may be carried out prior toand/or subsequent to insertion.

In some variations, the visual appearance of a support may be enhancedunder certain conditions to facilitate placement or to monitor theposition and/or condition of the support. Visual enhancement can beachieved by incorporating into or onto the support chromophores thatfluoresce or phosphoresce upon excitation with a light source.Chromophores may also assist a clinician in verifying the position ofthe support postoperatively using a gonioscope, for example. Lightsources can include lasers, lamps, and light-emitting diodes. In someinstances, transmission or absorption filters may be used to select thewavelength of the excitation source or to detect or view emission.Emission from a support capable of visual enhancement may be in thewavelength range of about 300 nm to about 800 nm. The chromophores maybe an integral component of the material making up the support, dopedinto support material, or coated or sprayed onto the support.Visually-enhancing chromophores may be applied on a temporary basis, oron a permanent basis. An example of a suitable chromophore isfluorescein, which may be excited with any laser or lamp emitting atabout 400 nm to about 500 nm. In addition, phosphorus-basedchemiluminescent or photoluminescent pigments may be used, which may beselected to absorb at various wavelengths across the visible spectrum.

In some variations, the support may be capable of being attached totissue. For example, the support may include a hook, loop, clip,extension, or the like that may be easily attached to tissue. Thesupport may also be attached to tissue using sutures or adhesives. Thesupport may be attached to tissue using more than one attachment method.For example, suturing may be used in combination with a loop, and/or anadhesive may be used in combination with a hook. In certain variations,a support may be allowed to self-position in Schlemm's canal. Forexample, a support, such as a helical or twisted support, may compriseone or more materials (e.g., shape-memory materials) that allow thesupport to be inserted into the canal in one configuration (e.g.,substantially straight and elongated) and to adjust to reconfigureitself within the canal (e.g., into a helical or twisted configuration).In some variations, a support may be mobile within Schlemm's canal.

Kits

Kits for reducing intraocular pressure are provided, where the kitscontain at least one support that may be implanted circumferentiallywithin Schlemm's canal, and that may be configured to restore ormaintain at least partial patency of at least a portion of Schlemm'scanal. The support may occupy at least a portion of a central core ofSchlemm's canal and/or may not substantially interfere with transmuralor transluminal flow across the canal, and/or with longitudinal flowwithin the canal. The kits may also provide an introducer or deliverydevice for implanting the support in the canal. The support andintroducer may be provided in a packaged combination in the kits. Thekits may also include instructions for use (e.g., for implanting andinspecting the support).

An introducer may be inserted into the eye and may be capable ofimplanting a support at the desired implantation position withinSchlemm's canal. For example, an introducer may include a tubularcannula through which a support may be passed. In addition to a cannula,an introducer may include a tubular or solid pusher rod that may be usedto push or advance the support into and/or around Schlemm's canal.Alternatively, a pusher rod or plunger may be used without a cannula tointroduce a support into the canal. A support may be installed into thelumen of a cannula prior to insertion, the distal end of the cannulapositioned at or near the desired support location, and the pusher rodoperated from the proximal end to push the support distally out of thedistal end of the cannula and into the canal. The cannula and/or pusherrod may be flexible and small enough in diameter to extend at leastpartially around the canal. In some variations, a proximal end of asuture may be introduced into the canal via a cannula and the sutureextended circumferentially around the canal. A distal portion of thesuture may be connected to the support and force applied to the proximalend of the suture to pull the support into the canal. The support maythen be positioned within the canal by pulling the suture in a distal orproximal direction. The suture may be used to anchor the support withinthe canal. In other variations, the support may be directly introducedinto the canal using surgical forceps, or the like.

FIGS. 24A-24D illustrate additional variations for introducing a supportinto Schlemm's canal. As shown in FIG. 24A, a support 200 may beintroduced into the canal using a syringe 202 and a plunger 204. Syringe202 has a distal end 206 that may be at least partially inserted into orplaced adjacent to an opening in the canal. Force in a distal directionmay be applied to plunger 204, thereby pushing support 200 into thecanal. Referring to FIGS. 24B and 24C, distal end 208 of guide element210 may be at least partially introduced into the canal. Guide element210 may comprise a guidewire. Guide element 210 may be extendedcircumferentially along the canal to aid in positioning the support.Support 212 comprises central bore 218 capable of accommodating guideelement 210 such that support 212 can be threaded onto guide element 210and slidably positioned along the guide element. Once distal end 209 ofsupport 212 is threaded onto guide element 210, support 212 may bepushed in a distal direction along guide element 210 to insert support212 into the canal. In some variations, support 212 may remain threadedonto guide element 210, and guide element 210 may remain in the canal.In other variations, support 212 may be slid off distal end 208 of guideelement 210, and the guide element may be pulled in a proximal directionfor removal. Referring to FIGS. 24C and 24D, syringe 202 with plunger204 may be used in combination with a guide element 210. In thisvariation, distal end 208 of guide element 210 may be inserted at leastpartially into Schlemm's canal. Guide element 210 may be extendedcircumferentially along the canal to aid in positioning the support.Support 212 has central bore 218 capable of accommodating guide element210. Proximal end 211 of guide element 210 may be inserted into bore218. Plunger 204 may be depressed in a distal direction to push support212 into the canal and slide support 212 along element 210. Guideelement 210 may remain in the canal or may be removed followinginsertion of the support. Supports 200 and 212 may be sufficientlyresilient to withstand force encountered as they are pushed into thecanal.

In some variations, a positioning device may be used with the introducerto position or adjust the support within the canal. A positioning devicemay include a rod, grippers, a clamp, a hook, or the like. In certainvariations, a device or system capable of dilating the canal tofacilitate insertion of a support may be included in the kits (e.g., asyringe or other device capable of injecting fluid into the canal).

In some variations, the kits may contain at least two supports. Multiplesupports may be implanted within one eye or within multiple eyes. If thekits contain multiple supports, the kits may also contain multipleintroducers. Alternatively, the same introducer may be used forimplantation of multiple supports, especially if the multiple supportsare being delivered to a single eye. If multiple supports are to bedelivered with the same introducer, then the multiple supports may bepreloaded into the introducer for sterility. If more than one support isincluded in a kit, the supports may be of different shapes, sizes,lengths, or materials. If the kits contain more than one support to beimplanted into a single eye, the supports may be connected together.

The kits may comprise one or more active agents, such as apharmaceutical agent. The active agent(s) may be included as an integralpart of the support, or may be supplied in kits for application to thesupport or to the eye during or after implantation. Examples of activeagents that may be supplied as part of the kits include prostaglandins,prostaglandin analogs, beta blockers, alpha-2 agonists, calcium channelblockers, carbonic anhydrase inhibitors, growth factors, such as tissuegrowth factors or vascular endothelial growth factors, anti-metabolites,chemotherapeutic agents such as mitomycin-C, 5-fluorouracil, steroids,antagonists of growth factors, such as antagonists of vascularendothelial growth factor, and combinations thereof.

The kits may contain a fixation device for attaching a support totissue. Such a fixation device may include sutures, hooks, barbs, clips,adhesives, and combinations thereof. In addition, the kits may include asystem for visually enhancing the support to facilitate viewing,positioning, and monitoring of a support. A system for visuallyenhancing the support may include a light source, a transmission orabsorption filter, a mirror, a composition comprising a chromophorecapable of fluorescing or phosphorescing that can be applied to thesupport, or any combination thereof. Chromophores may assist a clinicianin verifying the position of the support postoperatively using agonioscope, for example. The light source may be capable of exciting achromophore contained within or on the support such that the chromophoreemits fluorescence or phosphorescence. The emission is preferably withinthe wavelength range of about 300 nm to about 800 nm. A suitable lightsource for such a system may comprise a laser, a light emitting diode,or a lamp. In some instances, transmission or absorption filters may beused to further select the wavelength range of the excitation source orview or detect emission from chromophores. One or more minors may beused to direct a light source or emitted light, or to view the support.

Methods of Use

Methods for reducing intraocular pressure are also provided. In general,the methods may comprise inserting a support circumferentially within atleast a portion of Schlemm's canal, such that the support restores ormaintains at least partial patency of at least a portion of the canal.The support may or may not occupy at least a portion of a central coreof Schlemm's canal. In some variations, the support may notsubstantially interfere with transmural or transluminal flow acrossSchlemm's canal, and/or with longitudinal flow along the canal.

The methods may comprise inserting a support circumferentially intoSchlemm's canal using an introducer and/or a positioning device. Theintroducer may include a cannula and a tubular or hollow pusher rod oran advancing wire. The cannula may, for example, comprise a distal exitport having a cutting, beveled and/or tapered tip that allows thecannula to cut through the trabecular meshwork (e.g., if ab interno)and/or to be introduced into Schlemm's canal (e.g., for ab interno andab externo approaches). The support may be installed in the lumen of thecannula at its distal end and the pusher rod may be inserted into thelumen of the cannula at its proximal end and extended distally to pushthe support into position in the canal. In some instances, the cannulaand/or the pusher rod may be flexible and small enough in diameter to atleast partially extend circumferentially around the canal. In somevariations of the methods, a positioning device may be used in additionto an introducer. The positioning device may comprise a second rod, agripper, a hook, a clamp, or the like. Control of delivery oradvancement into Schlemm's canal may be via a more proximal control thatmay be operable from outside the eye.

In certain variations, the methods may include illuminating a supportwith a light source to cause the support to fluoresce or phosphoresce,thus aiding the visual appearance of the support. The illumination ofthe support may occur during and/or after implantation to inspect thesupport (e.g., to monitor its position, condition and/or performance).

In some instances, the methods may also comprise dilating Schlemm'scanal prior to and/or during insertion of the support. Dilation of thecanal may be accomplished by injecting fluid into the canal. Forexample, a high viscosity fluid such as sodium hyaluronate, or anotherviscoelastic substance or other dilating fluid known in the art, may beused to dilate the canal. As an example, in some variations, a fluid(e.g., a viscoelastic fluid) may be used first to dilate Schlemm'scanal, and then the support may be delivered into the canal. As anotherexample, in certain variations, a support may be packaged in a fluid(e.g., a viscoelastic fluid), and may be delivered (e.g., injected) intoSchlemm's canal concurrently with the fluid. As an additional example,in some variations, a support may be delivered into Schlemm's canal, anda fluid (e.g., a viscoelastic fluid) may be delivered (e.g., injected)into the canal after delivery of the support. In these cases the fluidmay, for example, help to push the support along within Schlemm's canal.

The methods may include implanting more than one support into an eye. Insome variations, the methods may include implanting two or more supportscircumferentially adjacent to each other within the canal. In certainvariations, the methods may include implanting supportscircumferentially opposed to each other within the canal (e.g., twosupports centered about 180° apart around the circumference of Schlemm'scanal). Some variations of the methods may comprise connecting togethermultiple supports in a single eye.

In some variations, the methods may include anchoring the support totissue surrounding Schlemm's canal. Anchoring the support to tissue maybe accomplished in a variety of ways (e.g., by suturing, application ofadhesives, installation of hooks, clips, or the like, or combinationsthereof). In certain variations, the methods may comprise selecting thesize of the support such that the support fits securely into the canalby a friction fit. Examples of arcuate supports that may be implantedwith a friction fit are illustrated in FIGS. 11A-11C.

The methods described here may also include altering the support usingelectromagnetic radiation. For example, a support may include regionscapable of preferentially absorbing a certain wavelength range. Whenelectromagnetic radiation of the appropriate wavelength range withsufficient energy is incident upon the support, material in thepreferentially absorbing regions may melt or ablate, resulting inperforations or indentations in the support at those regions. Forexample, a pulsed titanium sapphire laser emitting at about 750 nm toabout 800 nm incident on gold may cause the gold to melt or ablate. Thealteration of a support using electromagnetic radiation may occur beforeor after implantation of the support. For example, fenestrations may becreated or enlarged in a support after the support has remained in aneye for a period of time to enhance drainage.

Delivery of the supports described here may comprise an internalapproach (ab interno) or an external approach (ab externo), asappropriate.

In some variations, an external approach may comprise achieving accessto Schlemm's canal by cutting down to it from the sclera until it isdirectly visualized. The support may then be implanted. For example, theconjunctiva may be incised and a scleral flap may be created. Schlemm'scanal may be exposed and may be directly visualized (e.g., under amicroscope). The same delivery system as described for the internalapproach may be used; however, the external approach may not involvecutting through the trabecular meshwork.

In certain variations, an internal approach may comprise achievingaccess to Schlemm's canal by creating a full-thickness incision in thecornea, anterior most sclera, or corneoscleral junction (i.e. thecorneal limbus). Under endoscopic visualization, a combination ofgonioscopic and microscopic visualization, or just microscopicvisualization, a cutting blade or needle and a support or a deliverydevice containing a support may be passed through the anterior chamberto the trabecular meshwork. The trabecular meshwork may then be piercedor incised to allow eventual entry into the underlying lumen ofSchlemm's canal (e.g., by cutting a hole with a needle or blade,creating a hole with a laser, creating a hole with electrical current(i.e., electrocautery), creating a hole with the tip of the supportand/or delivery device, and/or using a delivery cannula that has acutting surface on its distal tip). As an example, a trocar that has acutting surface may be used to perforate the trabecular meshwork, and aguard or stop may be used to prevent over-insertion. As another example,a cannula for implant delivery could likewise have a cutting, taperedand/or beveled tip for piercing the trabecular meshwork prior toadvancement of the cannula partially or completely within the canal forsupport implantation. In cases in which a cannula is used, the cannulamay be inserted into Schlemm's canal by any appropriate amount, from 0millimeters to the entire length of the support, or more. The supportmay then be implanted. In cases in which lasers are employed, anyappropriate laser or lasers may be used, including but not limited to a308 nm Xenon Chloride excimer laser (e.g., delivered through a fiberoptic).

Upon achieving access to the canal, either by direct visualization(i.e., using an external approach) or by piercing the trabecularmeshwork (i.e., using an internal approach), implantation of the supportmay proceed. In certain variations, a support may be delivered in arelatively straight form that provides for relatively easy delivery. Thesupport may later assume a different shape (e.g., dictated by memory andtemperature). Implantation may be achieved using any of a variety ofdifferent approaches, or combinations thereof. In some variations, asupport may be directly pushed into Schlemm's canal using a forceps orspecialized instrument to grasp the support while not damaging it. Incertain variations, and as noted previously, a support may be containedin a cannula that may be partially or completely advanced into Schlemm'scanal.

Support delivery may be achieved, for example, using a manual control ora proximal delivery control in cases in which a cannula is used, that isexternal to the eye and that is operated by the surgeon and/or surgicalstaff. The control may be in the form of, for example, a handheldactuator mechanism. When a support is delivered out of a cannula, insome variations, just the tip of the cannula is positioned in Schlemm'scanal and the support is pushed out. In certain variations, a push-pullmechanism may be used to deliver a support from a cannula, whereby thecannula is pulled upon and the support is simultaneously pushed upon.Other non-limiting examples of tools that may be used to deliver asupport include syringes or syringes in combination with pushing wires.A cannula and/or a delivered support may extend from 0° to 360° aroundthe canal.

The support may then be delivered by a pusher wire that pushes thesupport into its resting place in the canal, and the cannula may beslowly withdrawn while the pusher wire holds the support in place,ultimately leaving the support unsheathed and resting in the canal.Alternatively or additionally, fluid pressure may be used to force thesupport out of the cannula. The support may, for example, have ablocking element at its end to capture the directional pressure of thefluid (e.g., like a sail). In some variations, a pusher wire may have ascrew mechanism allowing the support to be pushed in using a screwingmotion rather than a simple push (e.g., providing for relativelycontrolled delivery). In certain variations, a disengagement mechanismmay be used to release a support from a cannula. In some variations, acannula or support may have a tapered tip for facilitating delivery,dilating narrowed areas of Schlemm's canal, and piercing through septaethat block the canal.

In certain variations of delivery methods in which a cannula is used, aviscoelastic or other type of solution or drug or dye (e.g., afluorescent dye) may be injected from the cannula.

Cannulas used for delivery of supports described herein may in somecases have tips that are blunt, sharpened, tapered, or beveled, or thathave a cutting surface or a partially cutting surface or a combinationof these and/or any other suitable features (e.g., to facilitateinsertion into Schlemm's canal). Cannulas may be made out of metals(e.g., titanium), metal alloys (e.g., stainless steel or nickel-titaniumalloys such as Nitinol) and/or polymers (e.g., transparent polycarbonateor polypropylene, or any other suitable polymers). In certainvariations, a cannula may comprise one or more elements (e.g., at thedistal end of the cannula) configured to prevent excessive entry of thecannula. In other words, the element or elements would allow the cannulato perforate the trabecular meshwork, but not to go beyond and causedamage to Schlemm's canal (basically allowing only entry into Schlemm'scanal). For example, a cannula with a beveled tip may be used to piercethrough the trabecular meshwork, such that the bevel is completelywithin Schlemm's canal. However, a peg, pin or bump (or other element,such as a widening or tapering feature) on the cannula may preventfurther insertion. In some cases, a cannula may comprise markings todenote the extent of insertion. In some variations, an element orelements may allow the cannula to be advanced further, but to acontrolled length of insertion (e.g., that is equivalent to the lengthof the support). In certain variations, a cannula may be dyed or coloredand/or may be fluorescent (e.g., to enhance visibility). Cannulas mayhave any appropriate dimensions, and in some cases may have a length ofup to 2 or 3 inches, an external diameter of 10 microns to 800 microns,and/or an internal diameter of 20 microns to 780 microns. In somevariations, a cannula may be pre-curved. Cannulas for use with themethods described here may also be flexible.

In some cases during delivery, a support may be threaded over aguidewire that may fit into a lumen of the support or through periodicfenestrations along the length of the support. The guidewire and supportmay be inserted together at the same time, or the guidewire may beinserted first, followed by running the support over it. Additionalnon-limiting examples of tools and techniques that may be used todeliver a support include forceps and pullthrough techniques.

In some variations of methods, elements or features of a support thatare configured to contact an interior surface of Schlemm's canal may bespaced in such a way as to reduce the likelihood of one or more of theelements or features blocking one or more of the collector channels ofthe canal. In certain variations, a support may be rotated or otherwisemoved during and/or after delivery into Schlemm's canal, to limit orprevent collector channel blockage. Delivery accuracy and placement maybe monitored using one or more imaging techniques, such asultrasonography, radiographic techniques, X-ray fluoroscopy, and/orother high-resolution imaging techniques (e.g., high-resolutionultrasonography), as well as interventional techniques (e.g., employingcontrast material or dye or fluorescent material or dye).

In certain variations, a support may be at least partially coated with(e.g., embedded in) one or more biocompatible, dissolvable, orbioabsorbable materials which may provide several advantages. Possibleadvantages may include making the delivery of the support less traumaticto the eye (e.g., providing a silicone coating to minimize any traumathat may be associated with insertion of the support), protecting adelicate support structure during implantation and providing moredelivery column strength for pushing and/or insertion, and/or enhancingvisibility of the support during delivery (e.g., the material may becolored, may comprise chromophores, or may be fluorescent). In somevariations, the coating may serve as a carrier or depot for one or moresubstances. In certain variations, the coating material(s) may contain atherapeutic agent (e.g., a drug), such as an antiglaucoma medication(e.g., to reduce pressure), an antifibrotic agent and/or antimetabolite(e.g., to reduce scarring), or an anti-inflammatory agent (e.g., toreduce inflammation and/or pain). Examples of anti-inflammatory agentsinclude heparin, mitomycin, 5-fluorouracil, anti-metabolites andnon-steroidal anti-inflammatories. Examples of anti-glaucoma medicationsinclude prostaglandins, beta-blockers, alpha adrenergic agonists,carbonic anhydrase inhibitors, and miotics. The material(s) may absorbon their own or in an accelerated manner (e.g., using an outside energysource). In certain variations, a support tip or coating may compriseone or more bioabsorbable materials containing a drug that may beabsorbed within a certain time period (e.g., hours, days, weeks, ormonths) following insertion.

In cases in which multiple supports are delivered into Schlemm's canal,some or all of the supports may be delivered in the same procedure, orsupports may be delivered in two or more different procedures. Forexample, one or more supports may be delivered to an eye using a firstprocedure, and one or more supports may be delivered to the same eyeusing a second procedure that occurs at a later date (e.g., 1 day, 1week, 1 month, 1 year, 2 years, 3 years, 4 years, 5 years, etc. later).

In some cases, one or more supports described herein may be implanted inSchlemm's canal, and may be followed by one or more other treatments(e.g., surgery, medicine) at a later date. It is believed that use ofsupports described herein may advantageously improve the efficacy oflater procedures, such as later excimer laser trabeculostomy, lasertrabeculoplasty and other surgeries, and may also improve the efficacyof medications that are used at a later date.

Methods of Making

Any appropriate methods may be used to make the devices describedherein. For example, in some variations, a support may be formed bytwisting a substrate, such as a ribbon member. The substrate may, forexample, be twisted around a mandrel. In some cases, one end of thesubstrate may be held by a tool (e.g., a vise), while another end of thesubstrate is held or grasped by another tool (e.g., a similar vise) thatrotates to twist the substrate. Other non-limiting examples of methodsthat may be used to form the devices described herein include laseretching, lithography, and injection molding. As an example, in somevariations, a support may be created using a lithography metaldeposition process. As another example, in certain variations, a supportmay be formed by injecting a polymer into a prefabricated mold.

Devices, methods and kits for use with Schlemm's canal are alsodescribed, for example, in U.S. patent application Ser. No. 11/475,523(published as US 2007/0298068 A1), which is incorporated herein byreference in its entirety.

While the inventive devices, methods and kits have been described insome detail by way of illustration, such illustration is for purposes ofclarity of understanding only. It will be readily apparent to those ofordinary skill in the art in light of the teachings herein that certainchanges and modifications may be made thereto without departing from thespirit and scope of the appended claims.

As an example, it is envisioned that the devices, methods and kits maybe applied to nonhuman eyes to reduce intraocular pressure (e.g., indogs, cats, primates, or horses).

As another example, devices described herein may be positioned entirelywithin Schlemm's canal or only partially within Schlemm's canal. In somevariations, a device may be positioned so that it extends or protrudesinto the anterior chamber of the eye. For example, in certainvariations, a device may have a configuration like support 1400 of FIGS.14A and 14B, but may further include a bent or curved region that allowsthe support to protrude into the anterior chamber of the eye during use.Devices described herein may include any appropriate number of bent orcurved regions, which may be used to position the devices in anysuitable manner.

In some variations, devices comprising supports similar or identical tothose described previously may be used to provide a bypass function(e.g., in addition to maintaining or restoring transmural, transluminaland/or longitudinal flow of aqueous humor). In some such variations, theoperator (e.g., surgeon) may not fully insert the support, and maythereby allow a proximal portion of the support to be positioned in theanterior chamber (thereby serving as a bypass). In certain variations,after delivery of a support, the distal end of the support (which isinside Schlemm's canal) may be engaged with a hook or grasping device(tearing a small part of the overlying trabecular meshwork) and bentinward to the anterior chamber to provide the support with a bypassfunction. The proximal end of the support may not have been fullyinserted into Schlemm's canal and may thereby already be serving abypass function. Alternatively, the proximal end may have been fullyinserted. In some variations, a support may comprise a proximal endand/or distal end that is configured to protrude from Schlemm's canal atan angle between 0° and 180° (e.g., 90°), across the trabecularmeshwork, and into the anterior chamber. For example, the support mayhave an “L” shape. The proximal end of the support may serve a bypassfunction and may, for example, measure between about 10 microns andabout 3 millimeters. The proximal end may have the same shape orconfiguration as the body of the support, or may have a different shapeor configuration. In some cases, the proximal end may be in the form ofa coil, or may be tubular or partially tubular. In variations in whichthe support has an “L” shape or a similar shape, the support may bepackaged and/or delivered with one or more of the cannulas or otherdelivery devices described herein (e.g., bending upon exiting thecannula or delivery device, as a result of shape memory), or a cannulaor other delivery device may be slit to accommodate the proximal bypassportion of the support.

As an additional example, in some cases it may be desirable to stretchSchlemm's canal. In such cases, a device may be configured (e.g., sizedand shaped) to achieve such stretching when placed within the canal.

What is claimed is:
 1. A device for reducing intraocular pressurecomprising: a twisted ribbon member implantable circumferentially withinat least a portion of Schlemm's canal and configured to restore ormaintain at least partial patency of at least a portion of Schlemm'scanal, wherein the twisted ribbon member comprises a double helix havinga length, a first elongated edge, a second elongated edge, and a centrallongitudinal axis, the first and second elongated edges of the doublehelix being twisted along and about the central longitudinal axis, andcomprising a plurality of struts extending therebetween in a directionsubstantially normal to the central longitudinal axis, and wherein theplurality of struts define a plurality of fenestrations spaced along atleast a portion of the length of the twisted ribbon member.
 2. Thedevice of claim 1, wherein the first and second elongated edges areconfigured to contact an interior surface of Schlemm's canal when thedevice is implanted in Schlemm's canal.
 3. The device of claim 2,wherein the first and second elongated edges are configured tocontinuously contact the interior surface of Schlemm's canal when thedevice is implanted in Schlemm's canal.
 4. The device of claim 1,wherein the device does not substantially interfere with transmural flowacross Schlemm's canal when the device is implanted in Schlemm's canal.5. The device of claim 1, wherein the twisted ribbon member comprises ashape memory alloy.
 6. The device of claim 5, wherein the shape memoryalloy comprises a nickel-titanium alloy.
 7. The device of claim 1,wherein the twisted ribbon member comprises a metal alloy.
 8. The deviceof claim 7, wherein the metal alloy comprises stainless steel.
 9. Thedevice of claim 1, wherein the twisted ribbon member comprises a metal.10. The device of claim 9, wherein the metal comprises titanium.